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Mitophagy in human health, ageing and disease

Nature Metabolism volume 5, pages 2047–2061 (2023)Cite this article

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Abstract

Maintaining optimal mitochondrial function is a feature of health. Mitophagy removes and recycles damaged mitochondria and regulates the biogenesis of new, fully functional ones preserving healthy mitochondrial functions and activities. Preclinical and clinical studies have shown that impaired mitophagy negatively affects cellular health and contributes to age-related chronic diseases. Strategies to boost mitophagy have been successfully tested in model organisms, and, recently, some have been translated into clinics. In this Review, we describe the basic mechanisms of mitophagy and how mitophagy can be assessed in human blood, the immune system and tissues, including muscle, brain and liver. We outline mitophagy’s role in specific diseases and describe mitophagy-activating approaches successfully tested in humans, including exercise and nutritional and pharmacological interventions. We describe how mitophagy is connected to other features of ageing through general mechanisms such as inflammation and oxidative stress and forecast how strengthening research on mitophagy and mitophagy interventions may strongly support human health.

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Fig. 1: Schematic representation of mitophagy pathways.
Fig. 2: Disease conditions associated with altered mitophagy.
Fig. 3: Mitophagy dysfunction links to sterile inflammatory responses.

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References

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. Hallmarks of aging: an expanding universe. Cell 186, 243–278 (2023).

    PubMed  Google Scholar 

  4. López-Otín, C. & Kroemer, G. Hallmarks of health. Cell 184, 33–63 (2021).

    PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  6. Sandoval, H. et al. Essential role for Nix in autophagic maturation of erythroid cells. Nature 454, 232–235 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. McWilliams, T. G. et al. mito-QC illuminates mitophagy and mitochondrial architecture in vivo. J. Cell Biol. 214, 333–345 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Sun, N. et al. Measuring in vivo mitophagy. Mol. Cell 60, 685–696 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Sekine, S. & Youle, R. J. PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol. BMC Biol. 16, 2 (2018).

    PubMed  PubMed Central  Google Scholar 

  10. Terešak, P. et al. Regulation of PRKN-independent mitophagy. Autophagy 18, 24–39 (2022).

    PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Lee, Y., Lee, H.-Y., Hanna, R. A. & Gustafsson, Å. B. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of parkin in cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol. 301, H1924–H1931 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  15. Soubannier, V., Rippstein, P., Kaufman, B. A., Shoubridge, E. A. & McBride, H. M. Reconstitution of mitochondria derived vesicle formation demonstrates selective enrichment of oxidized cargo. PloS ONE 7, e52830 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Roberts, R. F., Tang, M. Y., Fon, E. A. & Durcan, T. M. Defending the mitochondria: the pathways of mitophagy and mitochondrial-derived vesicles. Int. J. Biochem. Cell Biol. 79, 427–436 (2016).

    CAS  PubMed  Google Scholar 

  17. Soubannier, V. et al. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr. Biol. 22, 135–141 (2012).

    CAS  PubMed  Google Scholar 

  18. McLelland, G.-L., Soubannier, V., Chen, C. X., McBride, H. M. & Fon, E. A. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 33, 282–295 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Nicolás-Ávila, J. A. et al. A network of macrophages supports mitochondrial homeostasis in the heart. Cell 183, 94–109 (2020).

    PubMed  Google Scholar 

  20. Liang, W. et al. Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired. Nat. Commun. 14, 5031 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Rosina, M. et al. Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue. Cell Metab. 34, 533–548 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Davis, C. O. et al. Transcellular degradation of axonal mitochondria. Proc. Natl Acad. Sci. USA 111, 9633–9638 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Melentijevic, I. et al. C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress. Nature 542, 367–371 (2017).

  24. Hao, T. et al. Hypoxia-reprogramed megamitochondrion contacts and engulfs lysosome to mediate mitochondrial self-digestion. Nat. Commun. 14, 4105 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Wu, W. et al. FUNDC1 regulates mitochondrial dynamics at the ER–mitochondrial contact site under hypoxic conditions. EMBO J. 35, 1368–1384 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Pryde, K. R., Smith, H. L., Chau, K.-Y. & Schapira, A. H. V. PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy. J. Cell Biol. 213, 163–171 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Oshima, Y. et al. Parkin-independent mitophagy via Drp1-mediated outer membrane severing and inner membrane ubiquitination. J. Cell Biol. 220, e202006043 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Munson, M. J. et al. GAK and PRKCD are positive regulators of PRKN-independent mitophagy. Nat. Commun. 12, 6101 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Ziviani, E. & Whitworth, A. J. How could parkin-mediated ubiquitination of mitofusin promote mitophagy? Autophagy 6, 660–662 (2010).

    PubMed  Google Scholar 

  31. Palikaras, K. & Tavernarakis, N. Mitochondrial homeostasis: the interplay between mitophagy and mitochondrial biogenesis. Exp. Gerontol. 56, 182–188 (2014).

    CAS  PubMed  Google Scholar 

  32. Cantó, C. & Auwerx, J. PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr. Opin. Lipidol. 20, 98–105 (2009).

    PubMed  PubMed Central  Google Scholar 

  33. Malik, N. et al. Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1. Science 380, eabj5559 (2023).

    CAS  PubMed  Google Scholar 

  34. Lionaki, E., Markaki, M., Palikaras, K. & Tavernarakis, N. Mitochondria, autophagy and age-associated neurodegenerative diseases: new insights into a complex interplay. Biochim. Biophys. Acta 1847, 1412–1423 (2015).

    CAS  PubMed  Google Scholar 

  35. Laker, R. C. et al. Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy. Nat. Commun. 8, 548 (2017).

    PubMed  PubMed Central  Google Scholar 

  36. Iorio, R., Celenza, G. & Petricca, S. Mitophagy: molecular mechanisms, new concepts on parkin activation and the emerging role of AMPK/ULK1 axis. Cells 11, 30 (2021).

    PubMed  PubMed Central  Google Scholar 

  37. D’Amico, D. et al. The RNA-binding protein PUM2 impairs mitochondrial dynamics and mitophagy during aging. Mol. Cell 73, 775–787 (2019).

    PubMed  PubMed Central  Google Scholar 

  38. Shin, H. J. et al. Pink1-mediated chondrocytic mitophagy contributes to cartilage degeneration in osteoarthritis. J. Clin. Med. 8, 1849 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Kuroda, Y. et al. Parkin enhances mitochondrial biogenesis in proliferating cells. Hum. Mol. Genet. 15, 883–895 (2006).

    CAS  PubMed  Google Scholar 

  40. Egan, B. & Zierath, J. R. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. 17, 162–184 (2013).

    CAS  PubMed  Google Scholar 

  41. Gaitanos, G. C., Williams, C., Boobis, L. H. & Brooks, S. Human muscle metabolism during intermittent maximal exercise. J. Appl. Physiol. 75, 712–719 (1993).

    CAS  PubMed  Google Scholar 

  42. Sin, J. et al. Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts. Autophagy 12, 369–380 (2016).

    CAS  PubMed  Google Scholar 

  43. Hong, X. et al. Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy. Cell Stem Cell 29, 1298–1314 (2022).

    CAS  Google Scholar 

  44. Leduc-Gaudet, J.-P. et al. Parkin overexpression attenuates sepsis-induced muscle wasting. Cells 9, 1454 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Leduc-Gaudet, J.-P. et al. Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice. Oncotarget 6, 17923–17937 (2015).

    PubMed  PubMed Central  Google Scholar 

  46. García-Prat, L. et al. Autophagy maintains stemness by preventing senescence. Nature 529, 37–42 (2016).

    PubMed  Google Scholar 

  47. Luan, P. et al. Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy. Sci. Transl. Med. 13, eabb0319 (2021).

    CAS  PubMed  Google Scholar 

  48. Ryu, D. et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat. Med. 22, 879–888 (2016).

    CAS  PubMed  Google Scholar 

  49. Fang, E. F. et al. Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway. Sci. Rep. 7, 46208 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. D’Amico, D. et al. Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis. Aging Cell 21, e13662 (2022).

    PubMed  PubMed Central  Google Scholar 

  51. Choi, S. et al. 31P magnetic resonance spectroscopy assessment of muscle bioenergetics as a predictor of gait speed in the Baltimore Longitudinal Study of Aging. J. Gerontol. A Biol. Sci. Med. Sci. 71, 1638–1645 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Zane, A. C. et al. Muscle strength mediates the relationship between mitochondrial energetics and walking performance. Aging Cell 16, 461–468 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Tian, Q. et al. Muscle mitochondrial energetics predicts mobility decline in well-functioning older adults: the Baltimore Longitudinal Study of Aging. Aging Cell 21, e13552 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Gouspillou, G. et al. Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans. FASEB J. 28, 1621–1633 (2014).

    CAS  PubMed  Google Scholar 

  55. Balan, E. et al. Regular endurance exercise promotes fission, mitophagy, and oxidative phosphorylation in human skeletal muscle independently of age. Front. Physiol. 10, 1088 (2019).

    PubMed  PubMed Central  Google Scholar 

  56. Crane, J. D., Devries, M. C., Safdar, A., Hamadeh, M. J. & Tarnopolsky, M. A. The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure. J. Gerontol. A Biol. Sci. Med. Sci. 65, 119–128 (2010).

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  58. Liu, L. et al. Mitophagy receptor FUNDC1 is regulated by PGC-1α/NRF1 to fine tune mitochondrial homeostasis. EMBO Rep. 22, e50629 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Drummond, M. J. et al. Downregulation of E3 ubiquitin ligases and mitophagy-related genes in skeletal muscle of physically inactive, frail older women: a cross-sectional comparison. J. Gerontol. A Biol. Sci. Med. Sci. 69, 1040–1048 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Picca, A. et al. Relationship between mitochondrial quality control markers, lower extremity tissue composition, and physical performance in physically inactive older adults. Cells 12, 183 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Askanas, V., Engel, W. K. & Nogalska, A. Sporadic inclusion-body myositis: a degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy. Biochim. Biophys. Acta 1852, 633–643 (2015).

    CAS  PubMed  Google Scholar 

  62. Rygiel, K. A. et al. Mitochondrial and inflammatory changes in sporadic inclusion body myositis. Neuropathol. Appl. Neurobiol. 41, 288–303 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Mangner, N. et al. Molecular mechanisms of diaphragm myopathy in humans with severe heart failure. Circ. Res. 128, 706–719 (2021).

    CAS  PubMed  Google Scholar 

  64. Ferrucci, L. et al. Transcriptomic and proteomic of gastrocnemius muscle in peripheral artery disease. Circ. Res. 132, 1428–1443 (2023).

    CAS  PubMed  Google Scholar 

  65. Murphy, E. et al. Mitochondrial function, biology, and role in disease: a scientific statement from the American Heart Association. Circ. Res. 118, 1960–1991 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Kubli, D. A. et al. Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J. Biol. Chem. 288, 915–926 (2013).

    CAS  PubMed  Google Scholar 

  67. Zhang, W., Siraj, S., Zhang, R. & Chen, Q. Mitophagy receptor FUNDC1 regulates mitochondrial homeostasis and protects the heart from I/R injury. Autophagy 13, 1080–1081 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Soh, J. E. C. et al. RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy. J. Biol. Chem. 299, 102993 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Sweet, M. E. et al. Transcriptome analysis of human heart failure reveals dysregulated cell adhesion in dilated cardiomyopathy and activated immune pathways in ischemic heart failure. BMC Genomics 19, 812 (2018).

    CAS  Google Scholar 

  70. Billia, F. et al. PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function. Proc. Natl Acad. Sci. USA 108, 9572–9577 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Wang, B. et al. AMPKα2 protects against the development of heart failure by enhancing mitophagy via PINK1 phosphorylation. Circ. Res. 122, 712–729 (2018).

    CAS  PubMed  Google Scholar 

  72. Rugarli, E. I. & Langer, T. Mitochondrial quality control: a matter of life and death for neurons. EMBO J. 31, 1336–1349 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Faitg, J. et al. 3D neuronal mitochondrial morphology in axons, dendrites, and somata of the aging mouse hippocampus. Cell Rep. 36, 109509 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Fiesel, F. C. et al. (Patho-)physiological relevance of PINK1-dependent ubiquitin phosphorylation. EMBO Rep. 16, 1114–1130 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Deng, Z., Sheehan, P., Chen, S. & Yue, Z. Is amyotrophic lateral sclerosis/frontotemporal dementia an autophagy disease? Mol. Neurodegener. 12, 90 (2017).

    PubMed  PubMed Central  Google Scholar 

  76. Castellazzi, M. et al. Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer’s disease and mild cognitive impairment. Sci. Rep. 9, 20009 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Fang, E. F. et al. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nat. Neurosci. 22, 401–412 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Du, F. et al. PINK1 signalling rescues amyloid pathology and mitochondrial dysfunction in Alzheimer’s disease. Brain 140, 3233–3251 (2017).

    PubMed  PubMed Central  Google Scholar 

  79. Kerr, J. S. et al. Mitophagy and Alzheimer’s disease: cellular and molecular mechanisms. Trends Neurosci. 40, 151–166 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Fleming, A. et al. The different autophagy degradation pathways and neurodegeneration. Neuron 110, 935–966 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Lautrup, S., Sinclair, D. A., Mattson, M. P. & Fang, E. F. NAD+ in brain aging and neurodegenerative disorders. Cell Metab. 30, 630–655 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Hou, X. et al. Mitophagy alterations in Alzheimer’s disease are associated with granulovacuolar degeneration and early tau pathology. Alzheimers Dement. 17, 417–430 (2020).

    PubMed  PubMed Central  Google Scholar 

  83. Xie, C. et al. Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Nat. Biomed. Eng. 6, 76–93 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Sorrentino, V. et al. Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity. Nature 552, 187–193 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Mizuno, Y., Hattori, N., Mori, H., Suzuki, T. & Tanaka, K. Parkin and Parkinson’s disease. Curr. Opin. Neurol. 14, 477–482 (2001).

    CAS  PubMed  Google Scholar 

  86. West, A. B. & Maidment, N. T. Genetics of parkin-linked disease. Hum. Genet. 114, 327–336 (2004).

    CAS  PubMed  Google Scholar 

  87. Kahle, P. J., Waak, J. & Gasser, T. DJ-1 and prevention of oxidative stress in Parkinson’s disease and other age-related disorders. Free Radic. Biol. Med. 47, 1354–1361 (2009).

    CAS  PubMed  Google Scholar 

  88. Hague, S. et al. Early-onset Parkinson’s disease caused by a compound heterozygous DJ-1 mutation. Ann. Neurol. 54, 271–274 (2003).

  89. Newman, L. E. & Shadel, G. S. Pink1/parkin link inflammation, mitochondrial stress, and neurodegeneration. J. Cell Biol. 217, 3327–3329 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Liu, J., Liu, W., Li, R. & Yang, H. Mitophagy in Parkinson’s disease: from pathogenesis to treatment. Cells 8, 712 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Watzlawik, J. O. et al. Sensitive ELISA-based detection method for the mitophagy marker p-S65-Ub in human cells, autopsy brain, and blood samples. Autophagy 17, 2613–2628 (2021).

    CAS  PubMed  Google Scholar 

  92. 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 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Markovinovic, A. et al. Optineurin in amyotrophic lateral sclerosis: multifunctional adaptor protein at the crossroads of different neuroprotective mechanisms. Prog. Neurobiol. 154, 1–20 (2017).

    CAS  PubMed  Google Scholar 

  94. Evans, C. S. & Holzbaur, E. L. F. Autophagy and mitophagy in ALS. Neurobiol. Dis. 122, 35–40 (2019).

    CAS  PubMed  Google Scholar 

  95. Liu, X. et al. TBK1 variants in Chinese patients with amyotrophic lateral sclerosis. Neurobiol. Aging 97, 149.e9–149.e15 (2021).

    CAS  PubMed  Google Scholar 

  96. Harding, O. et al. ALS- and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy. Proc. Natl Acad. Sci. USA 118, e2025053118 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Foster, A. D. & Rea, S. L. The role of sequestosome 1/p62 protein in amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis. Neural Regen. Res. 15, 2186–2194 (2020).

    PubMed  PubMed Central  Google Scholar 

  98. Soto-Heredero, G., Gómez de Las Heras, M. M., Gabandé-Rodríguez, E., Oller, J. & Mittelbrunn, M. Glycolysis—a key player in the inflammatory response. FEBS J. 287, 3350–3369 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Sun, L. et al. Lack of PINK1 alters glia innate immune responses and enhances inflammation-induced, nitric oxide-mediated neuron death. Sci. Rep. 8, 383 (2018).

    PubMed  PubMed Central  Google Scholar 

  100. Fülöp, T., Dupuis, G., Witkowski, J. M. & Larbi, A. The role of immunosenescence in the development of age-related diseases. Rev. Invest. Clin. 68, 84–91 (2016).

    PubMed  Google Scholar 

  101. Franceschi, C. et al. Immunobiography and the heterogeneity of immune responses in the elderly: a focus on inflammaging and trained immunity. Front. Immunol. 8, 982 (2017).

    PubMed  PubMed Central  Google Scholar 

  102. Phadwal, K. et al. A novel method for autophagy detection in primary cells: impaired levels of macroautophagy in immunosenescent T cells. Autophagy 8, 677–689 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Gerland, L.-M. et al. Autolysosomes accumulate during in vitro CD8+ T-lymphocyte aging and may participate in induced death sensitization of senescent cells. Exp. Gerontol. 39, 789–800 (2004).

    CAS  PubMed  Google Scholar 

  104. Bektas, A. et al. Age-associated changes in human CD4+ T cells point to mitochondrial dysfunction consequent to impaired autophagy. Aging 11, 9234–9263 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Raz, Y. et al. Activation-induced autophagy is preserved in CD4+ T-cells in familial longevity. J. Gerontol. A Biol. Sci. Med. Sci. 72, 1201–1206 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. McCormick, J. J. et al. The effect of aging on the autophagic and heat shock response in human peripheral blood mononuclear cells. Physiol. Int. 105, 247–256 (2018).

    CAS  PubMed  Google Scholar 

  107. Bensalem, J. et al. Basal autophagic flux measured in blood correlates positively with age in adults at increased risk of type 2 diabetes. GeroScience https://doi.org/10.1007/s11357-023-00884-5 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Martino, S. et al. Deficient mitophagy pathways in sickle cell disease. Br. J. Haematol. 193, 988–993 (2021).

    CAS  PubMed  Google Scholar 

  109. Apostolova, N., Vezza, T., Muntane, J., Rocha, M. & Víctor, V. M. Mitochondrial dysfunction and mitophagy in type 2 diabetes: pathophysiology and therapeutic targets. Antioxid. Redox Signal. 39, 278–320 (2023).

    CAS  PubMed  Google Scholar 

  110. Yamada, T. et al. Mitochondrial stasis reveals p62-mediated ubiquitination in parkin-independent mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab. 28, 588–604 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Liu, L. et al. Mitophagy and its contribution to metabolic and aging-associated disorders. Antioxid. Redox Signal. 32, 906–927 (2020).

    CAS  PubMed  Google Scholar 

  112. Eslam, M. et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J. Hepatol. 73, 202–209 (2020).

    PubMed  Google Scholar 

  113. Czaja, M. J. Function of autophagy in nonalcoholic fatty liver disease. Dig. Dis. Sci. 61, 1304–1313 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Undamatla, R. et al. Reduced mitophagy is an early feature of NAFLD and liver-specific PARKIN knockout hastens the onset of steatosis, inflammation and fibrosis. Sci. Rep. 13, 7575 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Hidvegi, T. et al. An autophagy-enhancing drug promotes degradation of mutant α1-antitrypsin Z and reduces hepatic fibrosis. Science 329, 229–232 (2010).

    CAS  PubMed  Google Scholar 

  116. Pastore, N. et al. Gene transfer of master autophagy regulator TFEB results in clearance of toxic protein and correction of hepatic disease in α-1-anti-trypsin deficiency. EMBO Mol. Med. 5, 397–412 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Qiang, X. et al. Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress. Biochem. Biophys. Res. Commun. 472, 603–609 (2016).

    CAS  PubMed  Google Scholar 

  118. Drake, J. C. et al. Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy. Proc. Natl Acad. Sci. USA 118, e2025932118 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Koliaki, C. et al. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab. 21, 739–746 (2015).

    CAS  PubMed  Google Scholar 

  120. Ma, X., McKeen, T., Zhang, J. & Ding, W.-X. Role and mechanisms of mitophagy in liver diseases. Cells 9, 837 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Gancheva, S., Jelenik, T., Álvarez-Hernández, E. & Roden, M. Interorgan metabolic crosstalk in human insulin resistance. Physiol. Rev. 98, 1371–1415 (2018).

    CAS  PubMed  Google Scholar 

  122. Liu, H.-Y. et al. Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia: inhibition of FoxO1-dependent expression of key autophagy genes by insulin. J. Biol. Chem. 284, 31484–31492 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Sidarala, V. et al. Mitophagy protects β cells from inflammatory damage in diabetes. JCI Insight 5, e141138 (2020).

    PubMed  PubMed Central  Google Scholar 

  124. Tong, M. et al. Alternative mitophagy protects the heart against obesity-associated cardiomyopathy. Circ. Res. 129, 1105–1121 (2021).

    CAS  PubMed  Google Scholar 

  125. Scheele, C. et al. Altered regulation of the PINK1 locus: a link between type 2 diabetes and neurodegeneration? FASEB J. 21, 3653–3665 (2007).

    CAS  PubMed  Google Scholar 

  126. Czajka, A. et al. Altered mitochondrial function, mitochondrial DNA and reduced metabolic flexibility in patients with diabetic nephropathy. EBioMedicine 2, 499–512 (2015).

    PubMed  PubMed Central  Google Scholar 

  127. Fabbri, E. et al. Insulin resistance is associated with reduced mitochondrial oxidative capacity measured by 31P-magnetic resonance spectroscopy in participants without diabetes from the Baltimore Longitudinal Study of Aging. Diabetes 66, 170–176 (2017).

    CAS  PubMed  Google Scholar 

  128. Guan, Y. et al. Mitophagy in carcinogenesis, drug resistance and anticancer therapeutics. Cancer Cell Int. 21, 350 (2021).

    PubMed  PubMed Central  Google Scholar 

  129. Cesari, R. et al. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25–q27. Proc. Natl Acad. Sci. USA 100, 5956–5961 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Letessier, A. et al. Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer. Oncogene 26, 298–307 (2007).

    CAS  PubMed  Google Scholar 

  131. Poulogiannis, G. et al. PARK2 deletions occur frequently in sporadic colorectal cancer and accelerate adenoma development in Apc mutant mice. Proc. Natl Acad. Sci. USA 107, 15145–15150 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Mustafa, M. F. et al. Expression of autophagy and mitophagy markers in breast cancer tissues. Front. Oncol. 11, 612009 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Giatromanolaki, A., Koukourakis, M. I., Gatter, K. C., Harris, A. L. & Sivridis, E. BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1α pathway and prognosis. J. Clin. Pathol. 61, 217–220 (2008).

    CAS  PubMed  Google Scholar 

  134. Rosenfeldt, M. T. et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature 504, 296–300 (2013).

    CAS  PubMed  Google Scholar 

  135. Poillet-Perez, L. & White, E. MDVs to the rescue: how autophagy-deficient cancer cells adapt to defective mitophagy. Dev. Cell 56, 2010–2012 (2021).

    CAS  PubMed  Google Scholar 

  136. Anderson, R. et al. Phase II trial of cytarabine and mitoxantrone with devimistat in acute myeloid leukemia. Nat. Commun. 13, 1673 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Tang, Y. et al. Targeting mitophagy to promote apoptosis is a potential therapeutic strategy for cancer. Autophagy 19, 1031–1033 (2023).

    CAS  PubMed  Google Scholar 

  138. Sies, H. & Jones, D. P. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat. Rev. Mol. Cell Biol. 21, 363–383 (2020).

    CAS  PubMed  Google Scholar 

  139. Deretic, V. & Levine, B. Autophagy balances inflammation in innate immunity. Autophagy 14, 243–251 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Galluzzi, L. & Vanpouille-Box, C. BAX and BAK at the gates of innate immunity. Trends Cell Biol. 28, 343–345 (2018).

    CAS  PubMed  Google Scholar 

  141. Kepp, O., Galluzzi, L. & Kroemer, G. Mitochondrial control of the NLRP3 inflammasome. Nat. Immunol. 12, 199–200 (2011).

    CAS  PubMed  Google Scholar 

  142. Kim, J., Kim, H.-S. & Chung, J. H. Molecular mechanisms of mitochondrial DNA release and activation of the cGAS–STING pathway. Exp. Mol. Med. 55, 510–519 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Li, M. et al. Surface-binding to cardiolipin nanodomains triggers cytochrome c pro-apoptotic peroxidase activity via localized dynamics. Structure 27, 806–815 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Pizzuto, M. & Pelegrin, P. Cardiolipin in immune signaling and cell death. Trends Cell Biol. 30, 892–903 (2020).

    CAS  PubMed  Google Scholar 

  146. Bueno, M. et al. PINK1 attenuates mtDNA release in alveolar epithelial cells and TLR9 mediated profibrotic responses. PloS ONE 14, e0218003 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Sliter, D. A. et al. Parkin and PINK1 mitigate STING-induced inflammation. Nature 561, 258–262 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Zhong, W. et al. Defective mitophagy in aged macrophages promotes mitochondrial DNA cytosolic leakage to activate STING signaling during liver sterile inflammation. Aging Cell 21, e13622 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Picca, A. et al. Circulating mitochondrial DNA at the crossroads of mitochondrial dysfunction and inflammation during aging and muscle wasting disorders. Rejuvenation Res. 21, 350–359 (2018).

    CAS  Google Scholar 

  150. Babbar, M., Basu, S., Yang, B., Croteau, D. L. & Bohr, V. A. Mitophagy and DNA damage signaling in human aging. Mech. Ageing Dev. 186, 111207 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Valentin-Vega, Y. A. et al. Mitochondrial dysfunction in ataxia–telangiectasia. Blood 119, 1490–1500 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Cleaver, J. E. Defective repair replication of DNA in xeroderma pigmentosum. Nature 218, 652–656 (1968).

    CAS  PubMed  Google Scholar 

  153. Fang, E. F. et al. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD+/SIRT1 reduction. Cell 157, 882–896 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Lautrup, S. et al. Studying Werner syndrome to elucidate mechanisms and therapeutics of human aging and age-related diseases. Biogerontology 20, 255–269 (2019).

    PubMed  Google Scholar 

  155. Fang, E. F. et al. NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair. Cell Metab. 24, 566–581 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Fang, E. F. et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat. Commun. 10, 5284 (2019).

    PubMed  PubMed Central  Google Scholar 

  157. Tarpey, M. D. et al. Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal. Mol. Metab. 6, 1597–1609 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Borges, I. B. P. et al. Exercise training attenuates ubiquitin–proteasome pathway and increases the genes related to autophagy on the skeletal muscle of patients with inflammatory myopathies. J. Clin. Rheumatol. 27, S224–S231 (2021).

    PubMed  Google Scholar 

  159. Schwalm, C., Deldicque, L. & Francaux, M. Lack of activation of mitophagy during endurance exercise in human. Med. Sci. Sports Exerc. 49, 1552–1561 (2017).

    PubMed  Google Scholar 

  160. Mesquita, P. H. C. et al. Acute and chronic effects of resistance training on skeletal muscle markers of mitochondrial remodeling in older adults. Physiol. Rep. 8, e14526 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Estébanez, B. et al. Effects of a resistance-training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects. Eur. J. Sport Sci. 19, 931–940 (2019).

    PubMed  Google Scholar 

  162. Pileggi, C. A. et al. Minimal adaptation of the molecular regulators of mitochondrial dynamics in response to unilateral limb immobilisation and retraining in middle-aged men. Eur. J. Appl. Physiol. 123, 249–260 (2023).

    CAS  PubMed  Google Scholar 

  163. Chung, K. W. & Chung, H. Y. The effects of calorie restriction on autophagy: role on aging intervention. Nutrients 11, 2923 (2019).

    PubMed  PubMed Central  Google Scholar 

  164. Gutiérrez-Casado, E. et al. The impact of aging, calorie restriction and dietary fat on autophagy markers and mitochondrial ultrastructure and dynamics in mouse skeletal muscle. J. Gerontol. A Biol. Sci. Med. Sci. 74, 760–769 (2019).

    PubMed  Google Scholar 

  165. Civitarese, A. E. et al. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med. 4, e76 (2007).

    PubMed  PubMed Central  Google Scholar 

  166. Menshikova, E. V. et al. Calorie restriction-induced weight loss and exercise have differential effects on skeletal muscle mitochondria despite similar effects on insulin sensitivity. J. Gerontol. A Biol. Sci. Med. Sci. 73, 81–87 (2018).

    CAS  Google Scholar 

  167. Shirakabe, A. et al. Evaluating mitochondrial autophagy in the mouse heart. J. Mol. Cell. Cardiol. 92, 134–139 (2016).

    CAS  PubMed  Google Scholar 

  168. Islam, H. et al. Increasing whole-body energetic stress does not augment fasting-induced changes in human skeletal muscle. Pflugers Arch. 473, 241–252 (2021).

    CAS  PubMed  Google Scholar 

  169. D’Amico, D. et al. Impact of the natural compound urolithin A on health, disease, and aging. Trends Mol. Med. 27, 687–699 (2021).

    PubMed  Google Scholar 

  170. Singh, A. et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep. Med. 3, 100633 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Denk, D. et al. Expansion of T memory stem cells with superior anti-tumor immunity by urolithin A-induced mitophagy. Immunity 55, 2059–2073 (2022).

    CAS  PubMed  Google Scholar 

  172. Vannini, N. et al. The NAD-booster nicotinamide riboside potently stimulates hematopoiesis through increased mitochondrial clearance. Cell Stem Cell 24, 405–418 (2019).

    CAS  Google Scholar 

  173. Dollerup, O. L. et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. J. Physiol. 598, 731–754 (2020).

    CAS  PubMed  Google Scholar 

  174. Remie, C. M. E. et al. Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. Am. J. Clin. Nutr. 112, 413–426 (2020).

    PubMed  PubMed Central  Google Scholar 

  175. Lapatto, H. A. K. et al. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Sci. Adv. 9, eadd5163 (2023).

    PubMed  PubMed Central  Google Scholar 

  176. Schroeder, S. et al. Dietary spermidine improves cognitive function. Cell Rep. 35, 108985 (2021).

    CAS  PubMed  Google Scholar 

  177. Makarov, M. & Korkotian, E. Differential role of active compounds in mitophagy and related neurodegenerative diseases. Toxins 15, 202 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Nieman, D. C. et al. Quercetin’s influence on exercise performance and muscle mitochondrial biogenesis. Med. Sci. Sports Exerc. 42, 338–345 (2010).

    CAS  PubMed  Google Scholar 

  179. Nieman, D. C. et al. Effects of quercetin and EGCG on mitochondrial biogenesis and immunity. Med. Sci. Sports Exerc. 41, 1467–1475 (2009).

    CAS  PubMed  Google Scholar 

  180. Chin, R. M. et al. Pharmacological PINK1 activation ameliorates pathology in Parkinson’s disease models. Preprint at bioRxiv https://doi.org/10.1101/2023.02.14.528378 (2023).

  181. Sadovnikova, I. S. et al. Nrf2/ARE activators improve memory in aged mice via maintaining of mitochondrial quality control of brain and the modulation of gut microbiome. Pharmaceuticals 14, 607 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Georgakopoulos, N. D. et al. Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy. Sci. Rep. 7, 10303 (2017).

    PubMed  PubMed Central  Google Scholar 

  183. Yao, Z. et al. A novel small-molecule activator of Sirtuin-1 induces autophagic cell death/mitophagy as a potential therapeutic strategy in glioblastoma. Cell Death Dis. 9, 767 (2018).

    Google Scholar 

  184. Seabright, A. P. et al. AMPK activation induces mitophagy and promotes mitochondrial fission while activating TBK1 in a PINK1–parkin independent manner. FASEB J. 34, 6284–6301 (2020).

    CAS  PubMed  Google Scholar 

  185. Bhansali, S., Bhansali, A., Dutta, P., Walia, R. & Dhawan, V. Metformin upregulates mitophagy in patients with T2DM: a randomized placebo-controlled study. J. Cell. Mol. Med. 24, 2832–2846 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Tufi, R. et al. High-content phenotypic screen to identify small molecule enhancers of parkin-dependent ubiquitination and mitophagy. SLAS Discov. 28, 73–87 (2023).

    CAS  PubMed  Google Scholar 

  187. Mottis, A., Herzig, S. & Auwerx, J. Mitocellular communication: shaping health and disease. Science 366, 827–832 (2019).

    CAS  PubMed  Google Scholar 

  188. Monzel, A. S., Enríquez, J. A. & Picard, M. Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction. Nat. Metab. 5, 546–562 (2023).

    PubMed  Google Scholar 

  189. Mahapatra, G. et al. Blood-based bioenergetic profiling reveals differences in mitochondrial function associated with cognitive performance and Alzheimer’s disease. Alzheimers Dement. 19, 1466–1478 (2023).

    CAS  PubMed  Google Scholar 

  190. Picca, A. et al. Extracellular vesicles and damage-associated molecular patterns: a Pandora’s box in health and disease. Front. Immunol. 11, 601740 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the president, C. Rinsch, and the CMO, A. Singh, of Amazentis for their helpful comments on the manuscript. We apologize for the omission of many relevant studies due to space constraints. The work was supported by the École Polytechnique Fédérale de Lausanne and grants from the European Research Council (ERC-AdG-787702) and the Swiss National Science Foundation (SNSF 31003A_179435). This work was supported in part by the Intramural Research Program of the National Institute on Aging, NIH, Baltimore, MD, USA.

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  1. These authors contributed equally: Anna Picca, Julie Faitg.

Authors and Affiliations

  1. Department of Medicine and Surgery, LUM University, Casamassima, Italy

    Anna Picca

  2. Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Rome, Italy

    Anna Picca

  3. Amazentis, EPFL Innovation Park, Lausanne, Switzerland

    Julie Faitg & Davide D’Amico

  4. Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

    Johan Auwerx

  5. Division of Intramural Research, National Institute on Aging, Baltimore, MD, USA

    Luigi Ferrucci

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Contributions

A.P. contributed to writing and revising the manuscript. J.F. contributed to writing and revising the manuscript. J.A. read and revised the manuscript. L.F. contributed to writing and revising the manuscript. D.D’A. contributed to writing and revising the manuscript.

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Correspondence to Luigi Ferrucci or Davide D’Amico.

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Competing interests

J.F. and D.D’A. are employees of Amazentis. J.A. is a founder and/or consultant of MitoBridge–Astellas, MetroBiotech, Amazentis, Vandria, OrsoBio and NOV Metapharma. A.P. and L.F. declare no conflict of interest.

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Nature Metabolism thanks Jonathan Brestoff, Evandro Fang and Alvaro Elorza for their contribution to the peer review of this work. Primary Handling Editor: Christoph Schmitt, in collaboration with the Nature Metabolism team.

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Picca, A., Faitg, J., Auwerx, J. et al. Mitophagy in human health, ageing and disease. Nat Metab 5, 2047–2061 (2023). https://doi.org/10.1038/s42255-023-00930-8

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