Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases

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Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases
  • Bootman, M. D. & Bultynck, G. Fundamentals of cellular calcium signaling: a primer. Cold Spring Harb. Perspect. Biol. 12, a038802 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Giorgi, C., Marchi, S. & Pinton, P. The machineries, regulation and cellular functions of mitochondrial calcium. Nat. Rev. Mol. Cell Biol. 19, 713–730 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Berridge, M. J., Lipp, P. & Bootman, M. D. The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol. 1, 11–21 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bagur, R. & Hajnóczky, G. Intracellular Ca2+ sensing: its role in calcium homeostasis and signaling. Mol. Cell 66, 780–788 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rossi, A., Pizzo, P. & Filadi, R. Calcium, mitochondria and cell metabolism: a functional triangle in bioenergetics. Biochim. Biophys. Acta Mol. Cell Res. 1866, 1068–1078 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Garbincius, J. F. & Elrod, J. W. Mitochondrial calcium exchange in physiology and disease. Physiol. Rev. 102, 893–992 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Matuz-Mares, D., González-Andrade, M., Araiza-Villanueva, M. G., Vilchis-Landeros, M. M. & Vázquez-Meza, H. Mitochondrial calcium: effects of its imbalance in disease. Antioxidants 11, 801 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Orrenius, S., Gogvadze, V. & Zhivotovsky, B. Calcium and mitochondria in the regulation of cell death. Biochem. Biophys. Res. Commun. 460, 72–81 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Giorgio, V., Guo, L., Bassot, C., Petronilli, V. & Bernardi, P. Calcium and regulation of the mitochondrial permeability transition. Cell Calcium 70, 56–63 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Perrone, M. et al. Calcium homeostasis in the control of mitophagy. Antioxid. Redox Signal 38, 581–598 (2023).

    CAS 
    PubMed 

    Google Scholar 

  • Pivovarova, N. B. & Andrews, S. B. Calcium-dependent mitochondrial function and dysfunction in neurons. FEBS J. 277, 3622–3636 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Brini, M., Calì, T., Ottolini, D. & Carafoli, E. Neuronal calcium signaling: function and dysfunction. Cell Mol. Life Sci. 71, 2787–2814 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Filadi, R. & Pizzo, P. Mitochondrial calcium handling and neurodegeneration: when a good signal goes wrong. Curr. Opin. Physiol. 17, 224–233 (2020).

    Article 

    Google Scholar 

  • Palikaras, K., Lionaki, E. & Tavernarakis, N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat. Cell Biol. 20, 1013–1022 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ploumi, C., Daskalaki, I. & Tavernarakis, N. Mitochondrial biogenesis and clearance: a balancing act. FEBS J. 284, 183–195 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Picca, A., Faitg, J., Auwerx, J., Ferrucci, L. & D’Amico, D. Mitophagy in human health, ageing and disease. Nat. Metab. 5, 2047–2061 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Onishi, M., Yamano, K., Sato, M., Matsuda, N. & Okamoto, K. Molecular mechanisms and physiological functions of mitophagy. EMBO J. 40, e104705 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bonifati, V. et al. Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7. Neurol. Sci. 23, s59–s60 (2002).

    Article 
    PubMed 

    Google Scholar 

  • Quinn, P. M. J., Moreira, P. I., Ambrósio, A. F. & Alves, C. H. PINK1/PARKIN signalling in neurodegeneration and neuroinflammation. Acta Neuropathol. Commun. 8, 189 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jin, S. M. et al. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J. Cell Biol. 191, 933–942 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Greene, A. W. et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep. 13, 378–385 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yamano, K. & Youle, R. J. PINK1 is degraded through the N-end rule pathway. Autophagy 9, 1758–1769 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu, Y. et al. The ubiquitination of PINK1 is restricted to its mature 52-kDa form. Cell Rep. 20, 30–39 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fedorowicz, M. A. et al. Cytosolic cleaved PINK1 represses Parkin translocation to mitochondria and mitophagy. EMBO Rep. 15, 86–93 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Okatsu, K. et al. A dimeric PINK1-containing complex on depolarized mitochondria stimulates Parkin recruitment. J. Biol. Chem. 288, 36372–36384 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jin, S. M. & Youle, R. J. The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria. Autophagy 9, 1750–1757 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Harbauer, A. B. et al. Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy. Neuron 110, 1516–1531.e1519 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hees, J. T. et al. Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons. Nat. Metab. 6, 514–530 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Di Rienzo, M. et al. AMBRA1 regulates mitophagy by interacting with ATAD3A and promoting PINK1 stability. Autophagy 18, 1752–1762 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Vives-Bauza, C. et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc. Natl Acad. Sci. USA 107, 378–383 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Narendra, D. P. et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 8, e1000298 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Matsuda, N. et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J. Cell Biol. 189, 211–221 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ordureau, A. et al. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol. Cell 56, 360–375 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wauer, T. et al. Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis. EMBO J. 34, 307–325 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kondapalli, C. et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2, 120080 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shiba-Fukushima, K. et al. PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci. Rep. 2, 1002 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Okatsu, K. et al. Phosphorylated ubiquitin chain is the genuine Parkin receptor. J. Cell Biol. 209, 111–128 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Okatsu, K. et al. PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat. Commun. 3, 1016 (2012).

    Article 
    PubMed 

    Google Scholar 

  • Kane, L. A. et al. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J. Cell Biol. 205, 143–153 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cai, Q., Zakaria, H. M., Simone, A. & Sheng, Z. H. Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons. Curr. Biol. 22, 545–552 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Durcan, T. M. & Fon, E. A. The three ‘P’s of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev. 29, 989–999 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Harper, J. W., Ordureau, A. & Heo, J.-M. Building and decoding ubiquitin chains for mitophagy. Nat. Rev. Mol. Cell Biol. 19, 93–108 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ziviani, E., Tao, R. N. & Whitworth, A. J. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc. Natl Acad. Sci. USA 107, 5018–5023 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gegg, M. E. et al. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum. Mol. Genet. 19, 4861–4870 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sun, Y., Vashisht, A. A., Tchieu, J., Wohlschlegel, J. A. & Dreier, L. Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy. J. Biol. Chem. 287, 40652–40660 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Geisler, S. et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol. 12, 119–131 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, X. et al. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147, 893–906 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fu, M. et al. Regulation of mitophagy by the Gp78 E3 ubiquitin ligase. Mol. Biol. Cell 24, 1153–1162 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, J. et al. Mitochondrial outer-membrane E3 ligase MUL1 ubiquitinates ULK1 and regulates selenite-induced mitophagy. Autophagy 11, 1216–1229 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Villa, E. et al. Parkin-independent mitophagy controls chemotherapeutic response in cancer cells. Cell Rep. 20, 2846–2859 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Szargel, R. et al. The PINK1, synphilin-1 and SIAH-1 complex constitutes a novel mitophagy pathway. Hum. Mol. Genet. 25, 3476–3490 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Di Rita, A. et al. HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα. Nat. Commun. 9, 3755 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Strappazzon, F. et al. Erratum: AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ. 22, 517–517 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lazarou, M. et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524, 309–314 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wong, Y. C. & Holzbaur, E. L. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc. Natl Acad. Sci. USA 111, E4439–E4448 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rasmussen, N. L., Kournoutis, A., Lamark, T. & Johansen, T. NBR1: the archetypal selective autophagy receptor. J. Cell Biol. 221, e202208092 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Heo, J. M., Ordureau, A., Paulo, J. A., Rinehart, J. & Harper, J. W. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol. Cell 60, 7–20 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Herhaus, L. TBK1 (TANK-binding kinase 1)-mediated regulation of autophagy in health and disease. Matrix Biol. 100-101, 84–98 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Heo, J. M. et al. RAB7A phosphorylation by TBK1 promotes mitophagy via the PINK-PARKIN pathway. Sci. Adv. 4, eaav0443 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tudorica, D. A. et al. A RAB7A phosphoswitch coordinates Rubicon Homology protein regulation of Parkin-dependent mitophagy. J. Cell Biol. 223, e202309015 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Herhaus, L. et al. TBK1‐mediated phosphorylation of LC3C and GABARAP‐L2 controls autophagosome shedding by ATG4 protease. EMBO Rep. 21, e48317 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Saha, B. et al. TBK1 is ubiquitinated by TRIM5α to assemble mitophagy machinery. Cell Rep. 43, 114294 (2024).

  • Zhang, J. & Ney, P. A. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ. 16, 939–946 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gao, A., Jiang, J., Xie, F. & Chen, L. Bnip3 in mitophagy: novel insights and potential therapeutic target for diseases of secondary mitochondrial dysfunction. Clin. Chim. Acta 506, 72–83 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Li, Y. et al. BNIP3L/NIX-mediated mitophagy: molecular mechanisms and implications for human disease. Cell Death Dis. 13, 14 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hanna, R. A. et al. Microtubule-associated protein 1 light chain 3 (LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy. J. Biol. Chem. 287, 19094–19104 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bellot, G. et al. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol. Cell Biol. 29, 2570–2581 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schiavi, A. et al. Iron-starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. Curr. Biol. 25, 1810–1822 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Schweers, R. L. et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc. Natl Acad. Sci. USA 104, 19500–19505 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Esteban-Martínez, L. et al. Programmed mitophagy is essential for the glycolytic switch during cell differentiation. EMBO J. 36, 1688–1706 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Simpson, C. L. et al. NIX initiates mitochondrial fragmentation via DRP1 to drive epidermal differentiation. Cell Rep. 34, 108689 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lampert, M. A. et al. BNIP3L/NIX and FUNDC1-mediated mitophagy is required for mitochondrial network remodeling during cardiac progenitor cell differentiation. Autophagy 15, 1182–1198 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yazdankhah, M. et al. BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes. Autophagy 17, 3140–3159 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu, K. et al. BNIP3 (BCL2 interacting protein 3) regulates pluripotency by modulating mitochondrial homeostasis via mitophagy. Cell Death Dis. 13, 334 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Poole, L. P., Bock-Hughes, A., Berardi, D. E. & Macleod, K. F. ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3. Sci. Rep. 11, 20526 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Park, C. W. et al. BNIP3 is degraded by ULK1-dependent autophagy via MTORC1 and AMPK. Autophagy 9, 345–360 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Marinković, M., Šprung, M. & Novak, I. Dimerization of mitophagy receptor BNIP3L/NIX is essential for recruitment of autophagic machinery. Autophagy 17, 1232–1243 (2021).

    Article 
    PubMed 

    Google Scholar 

  • Wei, L. et al. Dual-localized PPTC7 limits mitophagy through proximal and dynamic interactions with BNIP3 and NIX. Life Sci. Alliance 7, e202402765 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, T. et al. BNIP3 protein suppresses PINK1 kinase proteolytic cleavage to promote mitophagy. J. Biol. Chem. 291, 21616–21629 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ding, W. X. et al. Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J. Biol. Chem. 285, 27879–27890 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gao, F. et al. The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway. Hum. Mol. Genet. 24, 2528–2538 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Palikaras, K., Lionaki, E. & Tavernarakis, N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature 521, 525–528 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Delgado, J. M., Shepard, L. W., Lamson, S. W., Liu, S. L. & Shoemaker, C. J. The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover. EMBO J. 43, 32–60 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Liu, H. et al. The role of FUNDC1 in mitophagy, mitochondrial dynamics and human diseases. Biochem. Pharmacol. 197, 114891 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liu, L. et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat. Cell Biol. 14, 177–185 (2012).

    Article 
    PubMed 

    Google Scholar 

  • Wu, H. et al. The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy. Autophagy 10, 1712–1725 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu, W. et al. ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep. 15, 566–575 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, M. et al. Mitophagy receptor FUNDC1 regulates mitochondrial dynamics and mitophagy. Autophagy 12, 689–702 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Murakawa, T. et al. Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. Nat. Commun. 6, 7527 (2015).

    Article 
    PubMed 

    Google Scholar 

  • Murakawa, T. et al. A mammalian mitophagy receptor, Bcl2-L-13, recruits the ULK1 complex to induce mitophagy. Cell Rep. 26, 338–345.e336 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bhujabal, Z. et al. FKBP8 recruits LC3A to mediate Parkin‐independent mitophagy. EMBO Rep. 18, 947–961 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Saita, S., Shirane, M. & Nakayama, K. I. Selective escape of proteins from the mitochondria during mitophagy. Nat. Commun. 4, 1410 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Zhang, Y. et al. SPATA33 is an autophagy mediator for cargo selectivity in germline mitophagy. Cell Death Differ. 28, 1076–1090 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Panigrahi, D. P. et al. The inner mitochondrial membrane fission protein MTP18 serves as a mitophagy receptor to prevent apoptosis in oral cancer. J. Cell Sci. 136, jcs259986 (2023).

  • Wei, Y., Chiang, W. C., Sumpter, R. Jr, Mishra, P. & Levine, B. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell 168, 224–238.e210 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shu, L. et al. ATAD3B is a mitophagy receptor mediating clearance of oxidative stress-induced damaged mitochondrial DNA. EMBO J. 40, e106283 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chu, C. T. et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat. Cell Biol. 15, 1197–1205 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kagan, V. E. et al. NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy. Cell Death Differ. 23, 1140–1151 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • He, Y. et al. Phosphorylation of mitochondrial phospholipid scramblase 3 by protein kinase C-δ induces its activation and facilitates mitochondrial targeting of tBid. J. Cell. Biochem. 101, 1210–1221 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sentelle, R. D. et al. Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat. Chem. Biol. 8, 831–838 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Oleinik, N. et al. Mitochondrial protein import is regulated by p17/PERMIT to mediate lipid metabolism and cellular stress. Sci. Adv. 5, eaax1978 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Marín-García, J. in Heart Failure: Bench to Bedside, 171–194 (Humana Press, 2010).

  • Clapham, D. E. Calcium signaling. Cell 131, 1047–1058 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zajac, M. et al. A mechanism of lysosomal calcium entry. Sci. Adv. 10, eadk2317 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cooper, D. & Dimri, M. Biochemistry, Calcium Channels. StatPearls (StatPearls, 2024).

  • Fill, M. & Copello, J. A. Ryanodine receptor calcium release channels. Physiol. Rev. 82, 893–922 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Berridge, M. J. The inositol trisphosphate/calcium signaling pathway in health and disease. Physiol. Rev. 96, 1261–1296 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Woll, K. A. & Van Petegem, F. Calcium-release channels: structure and function of IP3 receptors and ryanodine receptors. Physiol. Rev. 102, 209–268 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Endo, M. Calcium-induced calcium release in skeletal muscle. Physiol. Rev. 89, 1153–1176 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Prakriya, M. & Lewis, R. S. Store-operated calcium channels. Physiol. Rev. 95, 1383–1436 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gao, J., Gao, A., Zhou, H. & Chen, L. The role of metal ions in the Golgi apparatus. Cell Biol. Int. 46, 1309–1319 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Pizzo, P., Lissandron, V., Capitanio, P. & Pozzan, T. Ca2+ signalling in the Golgi apparatus. Cell Calcium 50, 184–192 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Aulestia, F. J., Alonso, M. T. & García-Sancho, J. Differential calcium handling by the cis and trans regions of the Golgi apparatus. Biochem. J. 466, 455–465 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Christensen, K. A., Myers, J. T. & Swanson, J. A. pH-dependent regulation of lysosomal calcium in macrophages. J. Cell Sci. 115, 599–607 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Xu, H. & Ren, D. Lysosomal physiology. Annu. Rev. Physiol. 77, 57–80 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Scotto Rosato, A. et al. TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKβ/VPS34 pathway. Nat. Commun. 10, 5630 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Medina, D. L. et al. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat. Cell Biol. 17, 288–299 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Medina, D. L. Lysosomal calcium and autophagy. Int. Rev. Cell Mol. Biol. 362, 141–170 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Morgan, A. J., Platt, F. M., Lloyd-Evans, E. & Galione, A. Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease. Biochem. J. 439, 349–374 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Medina, D. L. et al. Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev. Cell 21, 421–430 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, X., Li, X. & Xu, H. Phosphoinositide isoforms determine compartment-specific ion channel activity. Proc. Natl Acad. Sci. USA 109, 11384–11389 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, X., Yu, L. & Xu, H. Lysosome calcium in ROS regulation of autophagy. Autophagy 12, 1954–1955 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Calcraft, P. J. et al. NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459, 596–600 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, X. et al. TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes. Cell 151, 372–383 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cang, C. et al. mTOR regulates lysosomal ATP-sensitive two-pore Na+ channels to adapt to metabolic state. Cell 152, 778–790 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gerndt, S. et al. Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function. Elife 9, e54712 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gerndt, S., Krogsaeter, E., Patel, S., Bracher, F. & Grimm, C. Discovery of lipophilic two-pore channel agonists. FEBS J. 287, 5284–5293 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yang, J., Zhao, Z., Gu, M., Feng, X. & Xu, H. Release and uptake mechanisms of vesicular Ca2+ stores. Protein Cell 10, 8–19 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Huang, P. et al. P2X4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH. J. Biol. Chem. 289, 17658–17667 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cao, Q. et al. Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion. J. Cell Biol. 209, 879–894 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Finkel, T. et al. The ins and outs of mitochondrial calcium. Circ. Res. 116, 1810–1819 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Denton, R. M. & McCormack, J. G. On the role of the calcium transport cycle in heart and other mammalian mitochondria. FEBS Lett. 119, 1–8 (1980).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Territo, P. R., Mootha, V. K., French, S. A. & Balaban, R. S. Ca2+ activation of heart mitochondrial oxidative phosphorylation: role of the F(0)/F(1)-ATPase. Am. J. Physiol. Cell Physiol. 278, C423–C435 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Colombini, M. VDAC: the channel at the interface between mitochondria and the cytosol. Mol. Cell Biochem. 256-257, 107–115 (2004).

    Article 
    PubMed 

    Google Scholar 

  • Camara, A. K. S., Zhou, Y., Wen, P. C., Tajkhorshid, E. & Kwok, W. M. Mitochondrial VDAC1: a key gatekeeper as potential therapeutic target. Front. Physiol. 8, 460 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Szabadkai, G. et al. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J. Cell Biol. 175, 901–911 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sassano, M. L., Felipe-Abrio, B. & Agostinis, P. ER-mitochondria contact sites; a multifaceted factory for Ca2+ signaling and lipid transport. Front. Cell Dev. Biol. 10, 988014 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Giacomello, M. & Pellegrini, L. The coming of age of the mitochondria-ER contact: a matter of thickness. Cell Death Differ. 23, 1417–1427 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dematteis, G. et al. ER-mitochondria distance is a critical parameter for efficient mitochondrial Ca2+ uptake and oxidative metabolism. Commun. Biol. 7, 1294 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Naón, D. et al. Splice variants of mitofusin 2 shape the endoplasmic reticulum and tether it to mitochondria. Science 380, eadh9351 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Filipe, A. et al. Defective endoplasmic reticulum-mitochondria contacts and bioenergetics in SEPN1-related myopathy. Cell Death Differ. 28, 123–138 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zito, E. & Ferreiro, A. Calcium and redox liaison: a key role of selenoprotein N in skeletal muscle. Cells 10, 1116 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kirichok, Y., Krapivinsky, G. & Clapham, D. E. The mitochondrial calcium uniporter is a highly selective ion channel. Nature 427, 360–364 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Broekemeier, K. M., Krebsbach, R. J. & Pfeiffer, D. R. Inhibition of the mitochondrial Ca2+ uniporter by pure and impure ruthenium red. Mol. Cell Biochem. 139, 33–40 (1994).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Matlib, M. A. et al. Oxygen-bridged dinuclear ruthenium amine complex specifically inhibits Ca2+ uptake into mitochondria in vitro and in situ in single cardiac myocytes. J. Biol. Chem. 273, 10223–10231 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sparagna, G. C., Gunter, K. K., Sheu, S. S. & Gunter, T. E. Mitochondrial calcium uptake from physiological-type pulses of calcium. A description of the rapid uptake mode. J. Biol. Chem. 270, 27510–27515 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Buntinas, L., Gunter, K. K., Sparagna, G. C. & Gunter, T. E. The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria. Biochim. Biophys. Acta 1504, 248–261 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bazil, J. N. & Dash, R. K. A minimal model for the mitochondrial rapid mode of Ca²+ uptake mechanism. PLoS ONE 6, e21324 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Raffaello, A. et al. The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J. 32, 2362–2376 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Oxenoid, K. et al. Architecture of the mitochondrial calcium uniporter. Nature 533, 269–273 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cao, C., Wang, S., Cui, T., Su, X. C. & Chou, J. J. Ion and inhibitor binding of the double-ring ion selectivity filter of the mitochondrial calcium uniporter. Proc. Natl Acad. Sci. USA 114, E2846–E2851 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Baradaran, R., Wang, C., Siliciano, A. F. & Long, S. B. Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters. Nature 559, 580–584 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee, S. K. et al. Structural insights into mitochondrial calcium uniporter regulation by divalent cations. Cell Chem. Biol. 23, 1157–1169 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bick, A. G., Calvo, S. E. & Mootha, V. K. Evolutionary diversity of the mitochondrial calcium uniporter. Science 336, 886 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Baughman, J. M. et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476, 341–345 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Plovanich, M. et al. MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS ONE 8, e55785 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Alevriadou, B. R. et al. Molecular nature and physiological role of the mitochondrial calcium uniporter channel. Am. J. Physiol. Cell Physiol. 320, C465–C482 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Csordás, G. et al. MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca2+ uniporter. Cell Metab. 17, 976–987 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mallilankaraman, K. et al. MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca2+ uptake that regulates cell survival. Cell 151, 630–644 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Patron, M. et al. MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol. Cell 53, 726–737 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kamer, K. J., Grabarek, Z. & Mootha, V. K. High-affinity cooperative Ca2+ binding by MICU1-MICU2 serves as an on-off switch for the uniporter. EMBO Rep. 18, 1397–1411 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Patron, M., Granatiero, V., Espino, J., Rizzuto, R. & De Stefani, D. MICU3 is a tissue-specific enhancer of mitochondrial calcium uptake. Cell Death Differ. 26, 179–195 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sancak, Y. et al. EMRE is an essential component of the mitochondrial calcium uniporter complex. Science 342, 1379–1382 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kovács-Bogdán, E. et al. Reconstitution of the mitochondrial calcium uniporter in yeast. Proc. Natl Acad. Sci. USA 111, 8985–8990 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yamamoto, T. et al. Analysis of the structure and function of EMRE in a yeast expression system. Biochim. Biophys. Acta 1857, 831–839 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tsai, M. F. et al. Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex. Elife 5, e15545 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Beutner, G., Sharma, V. K., Giovannucci, D. R., Yule, D. I. & Sheu, S. S. Identification of a ryanodine receptor in rat heart mitochondria. J. Biol. Chem. 276, 21482–21488 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Jakob, R. et al. Molecular and functional identification of a mitochondrial ryanodine receptor in neurons. Neurosci. Lett. 575, 7–12 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Beutner, G. et al. Type 1 ryanodine receptor in cardiac mitochondria: transducer of excitation-metabolism coupling. Biochim. Biophys. Acta 1717, 1–10 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Seidlmayer, L. K. et al. Inositol 1,4,5-trisphosphate-mediated sarcoplasmic reticulum-mitochondrial crosstalk influences adenosine triphosphate production via mitochondrial Ca2+ uptake through the mitochondrial ryanodine receptor in cardiac myocytes. Cardiovasc. Res. 112, 491–501 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Boyman, L., Williams, G. S., Khananshvili, D., Sekler, I. & Lederer, W. J. NCLX: the mitochondrial sodium calcium exchanger. J. Mol. Cell Cardiol. 59, 205–213 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shao, J. et al. Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca2+/H+ antiporter. Sci. Rep. 6, 34174 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Palty, R. et al. Lithium-calcium exchange is mediated by a distinct potassium-independent sodium-calcium exchanger. J. Biol. Chem. 279, 25234–25240 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kostic, M. & Sekler, I. Functional properties and mode of regulation of the mitochondrial Na+/Ca2+ exchanger, NCLX. Semin. Cell Dev. Biol. 94, 59–65 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kim, B. & Matsuoka, S. Cytoplasmic Na+-dependent modulation of mitochondrial Ca2+ via electrogenic mitochondrial Na+-Ca2+ exchange. J. Physiol. 586, 1683–1697 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Griffiths, E. J. Reversal of mitochondrial Na/Ca exchange during metabolic inhibition in rat cardiomyocytes. FEBS Lett. 453, 400–404 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Smets, I. et al. Ca2+ uptake in mitochondria occurs via the reverse action of the Na+/Ca2+ exchanger in metabolically inhibited MDCK cells. Am. J. Physiol. Ren. Physiol. 286, F784–F794 (2004).

    Article 
    CAS 

    Google Scholar 

  • Samanta, K., Mirams, G. R. & Parekh, A. B. Sequential forward and reverse transport of the Na+ Ca2+ exchanger generates Ca2+ oscillations within mitochondria. Nat. Commun. 9, 156 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tsai, M. F., Jiang, D., Zhao, L., Clapham, D. & Miller, C. Functional reconstitution of the mitochondrial Ca2+/H+ antiporter Letm1. J. Gen. Physiol. 143, 67–73 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jiang, D., Zhao, L., Clish, C. B. & Clapham, D. E. Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf-Hirschhorn syndrome. Proc. Natl Acad. Sci. USA 110, E2249–E2254 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jiang, D., Zhao, L. & Clapham, D. E. Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. Science 326, 144–147 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Waldeck-Weiermair, M. et al. Leucine zipper EF hand-containing transmembrane protein 1 (Letm1) and uncoupling proteins 2 and 3 (UCP2/3) contribute to two distinct mitochondrial Ca2+ uptake pathways. J. Biol. Chem. 286, 28444–28455 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hunter, D. R. & Haworth, R. A. The Ca2+-induced membrane transition in mitochondria. III. Transitional Ca2+ release. Arch. Biochem. Biophys. 195, 468–477 (1979).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Haworth, R. A. & Hunter, D. R. The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site. Arch. Biochem. Biophys. 195, 460–467 (1979).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hunter, D. R. & Haworth, R. A. The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms. Arch. Biochem. Biophys. 195, 453–459 (1979).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bernardi, P., Carraro, M. & Lippe, G. The mitochondrial permeability transition: recent progress and open questions. FEBS J. 289, 7051–7074 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Carraro, M. & Bernardi, P. The mitochondrial permeability transition pore in Ca2+ homeostasis. Cell Calcium 111, 102719 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bauer, T. M. & Murphy, E. Role of mitochondrial calcium and the permeability transition pore in regulating cell death. Circ. Res. 126, 280–293 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, W., Zhao, H. & Li, Y. Mitochondrial dynamics in health and disease: mechanisms and potential targets. Signal Transduct. Target. Ther. 8, 333 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Green, A., Hossain, T. & Eckmann, D. M. Mitochondrial dynamics involves molecular and mechanical events in motility, fusion and fission. Front. Cell Dev. Biol. 10, 1010232 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ni, H. M., Williams, J. A. & Ding, W. X. Mitochondrial dynamics and mitochondrial quality control. Redox Biol. 4, 6–13 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Saotome, M. et al. Bidirectional Ca2+-dependent control of mitochondrial dynamics by the Miro GTPase. Proc. Natl Acad. Sci. USA 105, 20728–20733 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Safiulina, D. et al. Miro proteins prime mitochondria for Parkin translocation and mitophagy. EMBO J. 38, e99384 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Safiulina, D., Kuum, M., Choubey, V., Hickey, M. A. & Kaasik, A. Mitochondrial transport proteins RHOT1 and RHOT2 serve as docking sites for PRKN-mediated mitophagy. Autophagy 15, 930–931 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, Y. & Sheng, Z. H. Kinesin-1-syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport. J. Cell Biol. 202, 351–364 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Grossmann, D. et al. Mutations in RHOT1 disrupt endoplasmic reticulum-mitochondria contact sites interfering with calcium homeostasis and mitochondrial dynamics in Parkinson’s disease. Antioxid. Redox Signal 31, 1213–1234 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, J.-Q. et al. Miro2 supplies a platform for Parkin translocation to damaged mitochondria. Sci. Bull. 64, 730–747 (2019).

    Article 
    CAS 

    Google Scholar 

  • Han, X.-J. et al. CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphology. J. Cell Biol. 182, 573–585 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cereghetti, G. M. et al. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc. Natl Acad. Sci. USA 105, 15803–15808 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zaninello, M., Palikaras, K., Sotiriou, A., Tavernarakis, N. & Scorrano, L. Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy. Cell Death Differ. 29, 167–177 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Favaro, G. et al. DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass. Nat. Commun. 10, 2576 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Park, K. et al. Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress. Nat. Commun. 13, 1300 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gandhi, S. et al. PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death. Mol. Cell 33, 627–638 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Akundi, R. S. et al. Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS ONE 6, e16038 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kostic, M. et al. PKA phosphorylation of NCLX reverses mitochondrial calcium overload and depolarization, promoting survival of PINK1-deficient dopaminergic neurons. Cell Rep. 13, 376–386 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Huang, E. et al. PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress. Nat. Commun. 8, 1399 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Doonan, P. J. et al. LETM1-dependent mitochondrial Ca2+ flux modulates cellular bioenergetics and proliferation. FASEB J. 28, 4936–4949 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Heeman, B. et al. Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance. J. Cell Sci. 124, 1115–1125 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dehvari, N. et al. Parkin-mediated ubiquitination regulates phospholipase C-γ1. J. Cell. Mol. Med. 13, 3061–3068 (2009).

    Article 
    PubMed 

    Google Scholar 

  • Sandebring, A. et al. Parkin deficiency disrupts calcium homeostasis by modulating phospholipase C signalling. FEBS J. 276, 5041–5052 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ham, S. J. et al. PINK1 and Parkin regulate IP3R-mediated ER calcium release. Nat. Commun. 14, 5202 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Calì, T., Ottolini, D., Negro, A. & Brini, M. Enhanced parkin levels favor ER-mitochondria crosstalk and guarantee Ca2+ transfer to sustain cell bioenergetics. Biochim. Biophys. Acta 1832, 495–508 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Marchesan, E. et al. Activation of Ca2+ phosphatase Calcineurin regulates Parkin translocation to mitochondria and mitophagy in flies. Cell Death Differ. 31, 217–238 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Matteucci, A. et al. Parkin-dependent regulation of the MCU complex component MICU1. Sci. Rep. 8, 14199 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Borbolis, F. & Palikaras, K. The compartmentalised nature of neuronal mitophagy: molecular insights and implications. Expert Rev. Mol. Med. 24, e38 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Evans, C. S. & Holzbaur, E. L. F. Quality control in neurons: mitophagy and other selective autophagy mechanisms. J. Mol. Biol. 432, 240–260 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Basak, B. & Holzbaur, E. L. F. Mitochondrial damage triggers concerted degradation of negative regulators of neuronal autophagy. Preprint at bioRxiv (2024).

  • Goldsmith, J., Ordureau, A., Harper, J. W. & Holzbaur, E. L. F. Brain-derived autophagosome profiling reveals the engulfment of nucleoid-enriched mitochondrial fragments by basal autophagy in neurons. Neuron 112, 520 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Martinez-Vicente, M. Neuronal mitophagy in neurodegenerative diseases. Front. Mol. Neurosci. 10, 64 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lou, G. et al. Mitophagy and neuroprotection. Trends Mol. Med. 26, 8–20 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Schrank, S., Barrington, N. & Stutzmann, G. E. Calcium-handling defects and neurodegenerative disease. Cold Spring Harb. Perspect. Biol. 12, a035212 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Verma, M., Lizama, B. N. & Chu, C. T. Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration. Transl. Neurodegener. 11, 3 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Markaki, M., Tsagkari, D. & Tavernarakis, N. Mitophagy and long-term neuronal homeostasis. J. Cell Sci. 136, jcs260638 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hardy, J., Duff, K., Hardy, K. G., Perez-Tur, J. & Hutton, M. Genetic dissection of Alzheimer’s disease and related dementias: amyloid and its relationship to tau. Nat. Neurosci. 1, 355–358 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, W., Zhao, F., Ma, X., Perry, G. & Zhu, X. Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Mol. Neurodegener. 15, 30 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ferreiro, E., Oliveira, C. R. & Pereira, C. M. F. The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway. Neurobiol. Dis. 30, 331–342 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sanz-Blasco, S., Valero, R. A., Rodríguez-Crespo, I., Villalobos, C. & Núñez, L. Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs. PLoS ONE 3, e2718 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Du, H. et al. Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model. Proc. Natl Acad. Sci. USA 107, 18670–18675 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Calvo-Rodriguez, M. et al. Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer’s disease. Nat. Commun. 11, 2146 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Britti, E., Ros, J., Esteras, N. & Abramov, A. Y. Tau inhibits mitochondrial calcium efflux and makes neurons vulnerable to calcium-induced cell death. Cell Calcium 86, 102150 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cummins, N., Tweedie, A., Zuryn, S., Bertran-Gonzalez, J. & Götz, J. Disease-associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria. EMBO J. 38, e99360 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Coffey, E. E., Beckel, J. M., Laties, A. M. & Mitchell, C. H. Lysosomal alkalization and dysfunction in human fibroblasts with the Alzheimer’s disease-linked presenilin 1 A246E mutation can be reversed with cAMP. Neuroscience 263, 111–124 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Neely Kayala, K. M. et al. Presenilin-null cells have altered two-pore calcium channel expression and lysosomal calcium: implications for lysosomal function. Brain Res. 1489, 8–16 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Morris, H. R., Spillantini, M. G., Sue, C. M. & Williams-Gray, C. H. The pathogenesis of Parkinson’s disease. Lancet 403, 293–304 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liss, B. & Surmeier, D. J. in Voltage-Gated Calcium Channels (eds Zamponi, G. W & Weiss, N.) 575–598 (Springer, 2022).

  • Leandrou, E., Emmanouilidou, E. & Vekrellis, K. Voltage-gated calcium channels and α-synuclein: implications in Parkinson’s disease. Front. Mol. Neurosci. 12, 237 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Parihar, M. S., Parihar, A., Fujita, M., Hashimoto, M. & Ghafourifar, P. Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells. Int. J. Biochem. Cell Biol. 41, 2015–2024 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Marongiu, R. et al. Mutant Pink1 induces mitochondrial dysfunction in a neuronal cell model of Parkinson’s disease by disturbing calcium flux. J. Neurochem. 108, 1561–1574 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bedford, C., Sears, C., Perez-Carrion, M., Piccoli, G. & Condliffe, S. B. LRRK2 regulates voltage-gated calcium channel function. Front. Mol. Neurosci. 9, 35 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee, K. S. et al. Altered ER-mitochondria contact impacts mitochondria calcium homeostasis and contributes to neurodegeneration in vivo in disease models. Proc. Natl Acad. Sci. USA 115, E8844–E8853 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bharat, V. et al. A mitochondrial inside-out iron-calcium signal reveals drug targets for Parkinson’s disease. Cell Rep. 42, 113544 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shaltouki, A., Hsieh, C. H., Kim, M. J. & Wang, X. Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson’s models. Acta Neuropathol. 136, 607–620 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hsieh, C. H. et al. Miro1 marks Parkinson’s disease subset and Miro1 reducer rescues neuron loss in Parkinson’s models. Cell Metab. 30, 1131–1140.e1137 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Soman, S. et al. Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in pink1(-/-) zebrafish. Eur. J. Neurosci. 45, 528–535 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Twyning, M. J. et al. Partial loss of MCU mitigates pathology in vivo across a diverse range of neurodegenerative disease models. Cell Rep. 43, 113681 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mejzini, R. et al. ALS genetics, mechanisms, and therapeutics: where are we now? Front. Neurosci. 13, 1310 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Smith, E. F., Shaw, P. J. & De Vos, K. J. The role of mitochondria in amyotrophic lateral sclerosis. Neurosci. Lett. 710, 132933 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Fuchs, A. et al. Selective mitochondrial Ca2+ uptake deficit in disease endstage vulnerable motoneurons of the SOD1G93A mouse model of amyotrophic lateral sclerosis. J. Physiol. 591, 2723–2745 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jaiswal, M. K. & Keller, B. U. Cu/Zn superoxide dismutase typical for familial amyotrophic lateral sclerosis increases the vulnerability of mitochondria and perturbs Ca2+ homeostasis in SOD1G93A mice. Mol. Pharm. 75, 478–489 (2009).

    Article 
    CAS 

    Google Scholar 

  • Coussee, E. et al. G37R SOD1 mutant alters mitochondrial complex I activity, Ca2+ uptake and ATP production. Cell Calcium 49, 217–225 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dafinca, R. et al. Impairment of mitochondrial calcium buffering links mutations in C9ORF72 and TARDBP in iPS-derived motor neurons from patients with ALS/FTD. Stem Cell Rep. 14, 892–908 (2020).

    Article 
    CAS 

    Google Scholar 

  • King, A. E., Woodhouse, A., Kirkcaldie, M. T. & Vickers, J. C. Excitotoxicity in ALS: overstimulation, or overreaction? Exp. Neurol. 275, 162–171 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tadić, V. et al. Investigation of mitochondrial calcium uniporter role in embryonic and adult motor neurons from G93A(hSOD1) mice. Neurobiol. Aging 75, 209–222 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Mühling, T., Duda, J., Weishaupt, J. H., Ludolph, A. C. & Liss, B. Elevated mRNA-levels of distinct mitochondrial and plasma membrane Ca2+ transporters in individual hypoglossal motor neurons of endstage SOD1 transgenic mice. Front. Cell Neurosci. 8, 353 (2014).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Jimenez-Sanchez, M., Licitra, F., Underwood, B. R. & Rubinsztein, D. C. Huntington’s disease: mechanisms of pathogenesis and therapeutic strategies. Cold Spring Harb. Perspect. Med. 7, a024240 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ross, C. A. & Tabrizi, S. J. Huntington’s disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. 10, 83–98 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tang, T. S. et al. Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron 39, 227–239 (2003).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Panov, A. V. et al. Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutamines. Nat. Neurosci. 5, 731–736 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lim, D. et al. Calcium homeostasis and mitochondrial dysfunction in striatal neurons of Huntington disease. J. Biol. Chem. 283, 5780–5789 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Panov, A. V., Lund, S. & Greenamyre, J. T. Ca2+-induced permeability transition in human lymphoblastoid cell mitochondria from normal and Huntington’s disease individuals. Mol. Cell Biochem. 269, 143–152 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shirendeb, U. P. et al. Mutant huntingtin’s interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington’s disease. Hum. Mol. Genet. 21, 406–420 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Martinez-Vicente, M. et al. Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease. Nat. Neurosci. 13, 567–576 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rui, Y. N., Xu, Z., Patel, B., Cuervo, A. M. & Zhang, S. HTT/Huntingtin in selective autophagy and Huntington disease: a foe or a friend within? Autophagy 11, 858–860 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sullivan, R., Yau, W. Y., O’Connor, E. & Houlden, H. Spinocerebellar ataxia: an update. J. Neurol. 266, 533–544 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Hisatsune, C., Hamada, K. & Mikoshiba, K. Ca2+ signaling and spinocerebellar ataxia. Biochim. Biophys. Acta Mol. Cell Res. 1865, 1733–1744 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • van de Leemput, J. et al. Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans. PLoS Genet. 3, e108 (2007).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Novak, M. J. et al. An ITPR1 gene deletion causes spinocerebellar ataxia 15/16: a genetic, clinical and radiological description. Mov. Disord. 25, 2176–2182 (2010).

    Article 
    PubMed 

    Google Scholar 

  • Dudding, T. E. et al. Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus. Neurology 63, 2288–2292 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tada, M., Nishizawa, M. & Onodera, O. Roles of inositol 1,4,5-trisphosphate receptors in spinocerebellar ataxias. Neurochem. Int. 94, 1–8 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Leung, T. C. S. et al. Mitochondrial damage and impaired mitophagy contribute to disease progression in SCA6. Acta Neuropathol. 147, 26 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Durcan, T. M. et al. The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability. Hum. Mol. Genet. 20, 141–154 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Harmuth, T. et al. Mitochondrial dysfunction in spinocerebellar ataxia type 3 is linked to VDAC1 deubiquitination. Int. J. Mol. Sci. 23, 5933 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wong, D. C. S. et al. OPA1 dominant optic atrophy: pathogenesis and therapeutic targets. J. Neuroophthalmol. 43, 464–474 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cipolat, S., Martins de Brito, O., Dal Zilio, B. & Scorrano, L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc. Natl Acad. Sci. USA 101, 15927–15932 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Frezza, C. et al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126, 177–189 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cartes-Saavedra, B. et al. OPA1 modulates mitochondrial Ca2+ uptake through ER-mitochondria coupling. Front. Cell Dev. Biol. 9, 774108 (2021).

    Article 
    PubMed 

    Google Scholar 

  • Zaninello, M. et al. Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy. Nat. Commun. 11, 4029 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

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