1932

Abstract

Maintaining mitochondrial health is essential for the survival and function of eukaryotic organisms. Misfunctioning mitochondria activate stress-responsive pathways to restore mitochondrial network homeostasis, remove damaged or toxic proteins, and eliminate damaged organelles via selective autophagy of mitochondria, a process termed mitophagy. Failure of these quality control pathways is implicated in the pathogenesis of Parkinson's disease and other neurodegenerative diseases. Impairment of mitochondrial quality control has been demonstrated to activate innate immune pathways, including inflammasome-mediated signaling and the antiviral cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)–regulated interferon response. Immune system malfunction is a common hallmark in many neurodegenerative diseases; however, whether inflammation suppresses or exacerbates disease pathology is still unclear. The goal of this review is to provide a historical overview of the field, describe mechanisms of mitochondrial quality control, and highlight recent advances on the emerging role of mitochondria in innate immunity and inflammation.

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2020-10-06
2024-05-23
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Literature Cited

  1. Ablasser A, Chen ZJ. 2019. cGAS in action: expanding roles in immunity and inflammation. Science 363:6431eaat8657
    [Google Scholar]
  2. Ablasser A, Schmid-Burgk JL, Hemmerling I, Horvath GL, Schmidt T et al. 2013. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature 503:7477530–34
    [Google Scholar]
  3. Agaisse H, Perrimon N. 2004. The roles of JAK/STAT signaling in Drosophila immune responses. Immunol. Rev. 198:72–82
    [Google Scholar]
  4. Alessi DR, Sammler E. 2018. LRRK2 kinase in Parkinson's disease. Science 360:638436–37
    [Google Scholar]
  5. Allen GFG, Toth R, James J, Ganley IG 2013. Loss of iron triggers PINK1/Parkin-independent mitophagy. EMBO Rep 14:121127–35
    [Google Scholar]
  6. Andreazza S, Samstag CL, Sanchez-Martinez A, Fernandez-Vizarra E, Gomez-Duran A et al. 2019. Mitochondrially-targeted APOBEC1 is a potent mtDNA mutator affecting mitochondrial function and organismal fitness in Drosophila. Nat. . Commun 10:3280
    [Google Scholar]
  7. Bobela W, Zheng L, Schneider BL 2014. Overview of mouse models of Parkinson's disease. Curr. Protoc. Mouse Biol. 4:3121–39
    [Google Scholar]
  8. Bonello F, Hassoun SM, Mouton-Liger F, Shin YS, Muscat A et al. 2019. LRRK2 impairs PINK1/Parkin-dependent mitophagy via its kinase activity: pathologic insights into Parkinson's disease. Hum. Mol. Genet. 28:101645–60
    [Google Scholar]
  9. Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ et al. 2003. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:5604256–59
    [Google Scholar]
  10. Boyer PD, Chance B, Ernster L, Mitchell P, Racker E, Slater EC 1977. Oxidative phosphorylation and photophosphorylation. Annu. Rev. Biochem. 46:955–66
    [Google Scholar]
  11. Bratic A, Kauppila TES, Macao B, Grönke S, Siibak T et al. 2015. Complementation between polymerase- and exonuclease-deficient mitochondrial DNA polymerase mutants in genomically engineered flies. Nat. Commun. 6:8808
    [Google Scholar]
  12. Brokatzky D, Dörflinger B, Haimovici A, Weber A, Kirschnek S et al. 2019. A non‐death function of the mitochondrial apoptosis apparatus in immunity. EMBO J 38:11e2018100907
    [Google Scholar]
  13. Buchon N, Silverman N, Cherry S 2014. Immunity in Drosophila melanogaster—from microbial recognition to whole-organism physiology. Nat. Rev. Immunol. 14:12796–810
    [Google Scholar]
  14. Burman JL, Pickles S, Wang C, Sekine S, Vargas JNS et al. 2017. Mitochondrial fission facilitates the selective mitophagy of protein aggregates. J. Cell Biol. 216:103231–47
    [Google Scholar]
  15. Carneiro LAM, Travassos LH, Girardin SE 2007. Nod-like receptors in innate immunity and inflammatory diseases. Ann. Med. 39:8581–93
    [Google Scholar]
  16. Carp H. 1982. Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils. J. Exp. Med. 155:1264–75
    [Google Scholar]
  17. Castanier C, Garcin D, Vazquez A, Arnoult D 2010. Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway. EMBO Rep 11:2133–38
    [Google Scholar]
  18. Cha GH, Kim S, Park J, Lee E, Kim M et al. 2005. Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. . PNAS 102:2910345–50
    [Google Scholar]
  19. Cho JH, Park JH, Chung CG, Shim H-J, Jeon KH et al. 2015. Parkin-mediated responses against infection and wound involve TSPO-VDAC complex in Drosophila. Biochem. Biophys. Res. Commun 463:1–21–6
    [Google Scholar]
  20. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR et al. 2006. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. . Nature 441:70971162–66Established that pink1 functions epistatically with parkin; published concurrently with Park et al. (2006).
    [Google Scholar]
  21. Cornelissen T, Vilain S, Vints K, Gounko N, Verstreken P, Vandenberghe W 2018. Deficiency of parkin and pink1 impairs age-dependent mitophagy in Drosophila. eLife 7:e35878
    [Google Scholar]
  22. Deng H, Dodson MW, Huang H, Guo M 2008. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. . PNAS 105:3814503–8
    [Google Scholar]
  23. Deng P, Naresh NU, Du Y, Lamech LT, Yu J et al. 2019. Mitochondrial UPR repression during Pseudomonas aeruginosa infection requires the bZIP protein ZIP-3. PNAS 116:136146–51
    [Google Scholar]
  24. Dhir A, Dhir S, Borowski LS, Jimenez L, Teitell M et al. 2018. Mitochondrial double-stranded RNA triggers antiviral signaling in humans. Nature 560:7717238–42
    [Google Scholar]
  25. Dolezal P, Likic V, Tachezy J, Lithgow T 2006. Evolution of the molecular machines for protein import into mitochondria. Science 313:5785314–18
    [Google Scholar]
  26. Dyall SD, Brown MT, Johnson PJ 2004. Ancient invasions: from endosymbionts to organelles. Science 304:5668253–57
    [Google Scholar]
  27. Dzamko N, Geczy CL, Halliday GM 2015. Inflammation is genetically implicated in Parkinson's disease. Neuroscience 302:89–102
    [Google Scholar]
  28. Fiorese CJ, Schulz AM, Lin YF, Rosin N, Pellegrino MW, Haynes CM 2016. The transcription factor ATF5 mediates a mammalian mitochondrial UPR. Curr. Biol. 26:152037–43
    [Google Scholar]
  29. Frank-Cannon TC, Tran T, Ruhn KA, Martinez TN, Hong J et al. 2008. Parkin deficiency increases vulnerability to inflammation-related nigral degeneration. J. Neurosci. 28:4310825–34
    [Google Scholar]
  30. Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK 2011. ER tubules mark sites of mitochondrial division. Science 334:6054358–62
    [Google Scholar]
  31. Funayama M, Ohe K, Amo T et al. 2015. CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study. Lancet Neurol 14:3274–82
    [Google Scholar]
  32. Gao K, Li Y, Hu S, Liu Y 2019. SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity and lifespan extension. eLife 8:e41792
    [Google Scholar]
  33. Giannoccaro MP, La Morgia C, Rizzo G, Carelli V 2017. Mitochondrial DNA and primary mitochondrial dysfunction in Parkinson's disease. Mov. Disord. 32:3346–63
    [Google Scholar]
  34. Glauser L, Sonnay S, Stafa K, Moore DJ 2011. Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor Mitofusin1. J. Neurochem. 118:4636–45
    [Google Scholar]
  35. Goto A, Okado K, Martins N, Cai H, Barbier V et al. 2018. The kinase IKKβ regulates a STING- and NF-κB-dependent antiviral response pathway in Drosophila. . Immunity 49:2225–34.e4
    [Google Scholar]
  36. Gottlieb E, Armour SM, Harris MH, Thompson CB 2003. Mitochondrial membrane potential regulates matrix configuration and cytochrome c release during apoptosis. Cell Death Differ 10:6709–17
    [Google Scholar]
  37. Greene JC, Whitworth AJ, Andrews LA, Parker TJ, Pallanck LJ 2005. Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Hum. Mol. Genet. 14:6799–811
    [Google Scholar]
  38. Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ 2003. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. PNAS 100:74078–83First description of fly parkin mutants, establishing a role for Parkin in mitochondrial homeostasis.
    [Google Scholar]
  39. Gui X, Yang H, Li T, Tan X, Shi P et al. 2019. Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature 567:7747262–66
    [Google Scholar]
  40. Hammond TR, Marsh SE, Stevens B 2019. Immune signaling in neurodegeneration. Immunity 50:4955–74
    [Google Scholar]
  41. Hatefi Y. 1985. The mitochondrial electron transport and oxidative phosphorylation system. Annu. Rev. Biochem. 54:1015–69
    [Google Scholar]
  42. He Y, Hara H, Núñez G 2016. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem. Sci. 41:121012–21
    [Google Scholar]
  43. Heo JM, Ordureau A, Paulo JA, Rinehart J, Harper JW 2015. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol. Cell 60:17–20
    [Google Scholar]
  44. Hill JH, Chen Z, Xu H 2014. Selective propagation of functional mitochondrial DNA during oogenesis restricts the transmission of a deleterious mitochondrial variant. Nat. Genet. 46:4389–92
    [Google Scholar]
  45. Hoppins S, Lackner L, Nunnari J 2007. The machines that divide and fuse mitochondria. Annu. Rev. Biochem. 76:751–80
    [Google Scholar]
  46. Hsu YT, Wolter KG, Youle RJ 1997. Cytosol-to-membrane redistribution of Bax and Bcl-XL during apoptosis. PNAS 94:83668–72
    [Google Scholar]
  47. Hubert V, Peschel A, Langer B, Gröger M, Rees A, Kain R 2016. LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes. Biol. Open 5:101516–29
    [Google Scholar]
  48. Hughes AL, Hughes CE, Henderson KA, Yazvenko N, Gottschling DE 2016. Selective sorting and destruction of mitochondrial membrane proteins in aged yeast. eLife 5:e13943
    [Google Scholar]
  49. Ishikawa H, Ma Z, Barber GN 2009. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461:7265788–92
    [Google Scholar]
  50. Issa A-R, Sun J, Petitgas C, Mesquita A, Dulac A et al. 2018. The lysosomal membrane protein LAMP2A promotes autophagic flux and prevents SNCA-induced Parkinson disease-like symptoms in the Drosophila brain. Autophagy 14:111898–910
    [Google Scholar]
  51. Iyer SS, He Q, Janczy JR, Elliott EI, Zhong Z et al. 2013. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 39:2311–23
    [Google Scholar]
  52. Jin SM, Youle RJ. 2013. The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria. Autophagy 9:111750–57
    [Google Scholar]
  53. Johansen T, Lamark T. 2011. Selective autophagy mediated by autophagic adapter proteins. Autophagy 7:3279–96
    [Google Scholar]
  54. Kalia LV, Lang AE. 2015. Parkinson's disease. Lancet 386:9996896–912
    [Google Scholar]
  55. Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K et al. 2014. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J. Cell Biol. 205:2143–53
    [Google Scholar]
  56. Kanneganti TD, Lamkanfi M, Núñez G 2007. Intracellular NOD-like receptors in host defense and disease. Immunity 27:4549–59
    [Google Scholar]
  57. Karbowski M, Youle RJ. 2011. Regulating mitochondrial outer membrane proteins by ubiquitination and proteasomal degradation. Curr. Opin. Cell Biol. 23:4476–82
    [Google Scholar]
  58. Katayama H, Hama H, Nagasawa K, Kurokawa H, Sugiyama M et al. 2020. Visualizing and modulating mitophagy for therapeutic studies of neurodegeneration. Cell 181:51176–87.e16
    [Google Scholar]
  59. Katayama H, Kogure T, Mizushima N, Yoshimori T, Miyawaki A 2011. A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery. Chem. Biol. 18:81042–52
    [Google Scholar]
  60. Kauppila TES, Bratic A, Jensen MB, Baggio F, Partridge L et al. 2018. Mutations of mitochondrial DNA are not major contributors to aging of fruit flies. PNAS 115:41E9620–29
    [Google Scholar]
  61. Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS et al. 2014. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem. J. 460:1127–41
    [Google Scholar]
  62. Khan NA, Nikkanen J, Yatsuga S, Jackson C, Wang L et al. 2017. mTORC1 regulates mitochondrial integrated stress response and mitochondrial myopathy progression. Cell Metab 26:2419–28.e5
    [Google Scholar]
  63. Kim J, Gupta R, Blanco LP, Yang S, Shteinfer-Kuzmine A et al. 2019. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science 366:64721531–36
    [Google Scholar]
  64. Kim YY, Um J-H, Yoon J-H, Kim H, Lee D-Y et al. 2019. Assessment of mitophagy in mt-Keima Drosophila revealed an essential role of the PINK1-Parkin pathway in mitophagy induction in vivo. . FASEB J 33:99742–51
    [Google Scholar]
  65. Kirienko NV, Ausubel FM, Ruvkun G 2015. Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa. . PNAS 112:61821–26
    [Google Scholar]
  66. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y et al. 1998. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:6676605–8First report of parkin mutations in early-onset recessive Parkinson's disease.
    [Google Scholar]
  67. Kitada T, Tong Y, Gautier CA, Shen J 2009. Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout mice. J. Neurochem. 111:3696–702
    [Google Scholar]
  68. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD 1997. The release of cytochrome c from mitochondria: a primary site for Bcl- 2 regulation of apoptosis. Science 275:53031132–36
    [Google Scholar]
  69. Koehler CL, Perkins GA, Ellisman MH, Jones DL 2017. Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging. J. Cell Biol. 216:82315–27
    [Google Scholar]
  70. Koppen M, Langer T. 2007. Protein degradation within mitochondria: versatile activities of AAA proteases and other peptidases. Crit. Rev. Biochem. Mol. Biol. 42:3221–42
    [Google Scholar]
  71. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E et al. 2014. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510:7503162–66
    [Google Scholar]
  72. Koyano F, Yamano K, Kosako H, Tanaka K, Matsuda N 2019. Parkin recruitment to impaired mitochondria for nonselective ubiquitylation is facilitated by MITOL. J. Biol. Chem. 294:2610300–14
    [Google Scholar]
  73. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C et al. 2015. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:7565309–14
    [Google Scholar]
  74. Le Guerroué F, Eck F, Jung J, Starzetz T, Mittelbronn M et al. 2017. Autophagosomal content profiling reveals an LC3C-dependent piecemeal mitophagy pathway. Mol. Cell 68:4786–96.e6
    [Google Scholar]
  75. Lee JJ, Sanchez-Martinez A, Zarate AM, Benincá C, Mayor U et al. 2018. Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or Parkin. J. Cell Biol. 217:51613–22
    [Google Scholar]
  76. Lemasters JJ. 2005. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res 8:13–5
    [Google Scholar]
  77. Lemasters JJ, Nieminen A-L, Qian T, Trost LC, Elmore SP et al. 1998. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim. Biophys. Acta Bioenerg. 1366:1–2177–96
    [Google Scholar]
  78. Lieber T, Jeedigunta SP, Palozzi JM, Lehmann R, Hurd TR 2019. Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline. Nature 570:7761380–84
    [Google Scholar]
  79. Liston A, Masters SL. 2017. Homeostasis-altering molecular processes as mechanisms of inflammasome activation. Nat. Rev. Immunol. 17:3208–14
    [Google Scholar]
  80. Liu Y, Gordesky-Gold B, Leney-Greene M, Weinbren NL, Tudor M, Cherry S 2018. Inflammation-induced, STING-dependent autophagy restricts Zika virus infection in the Drosophila brain. Cell Host Microbe 24:157–68.e3
    [Google Scholar]
  81. Liu Y, Olagnier D, Lin R 2017. Host and viral modulation of RIG-I-mediated antiviral immunity. Front. Immunol. 7:663
    [Google Scholar]
  82. Lugrin J, Martinon F. 2018. The AIM2 inflammasome: sensor of pathogens and cellular perturbations. Immunol. Rev. 281:199–114
    [Google Scholar]
  83. Luteijn RD, Zaver SA, Gowen BG, Wyman SK, Garelis NE et al. 2019. SLC19A1 transports immunoreactive cyclic dinucleotides. Nature 573:7774434–38
    [Google Scholar]
  84. Ma H, Xu H, O'Farrell PH 2014. Transmission of mitochondrial mutations and action of purifying selection in Drosophila melanogaster. Nat. . Genet 46:4393–97
    [Google Scholar]
  85. Ma P, Yun J, Deng H, Guo M 2018. Atg1-mediated autophagy suppresses tissue degeneration in pink1/parkin mutants by promoting mitochondrial fission in Drosophila. Mol. Biol. . Cell 29:263082–92
    [Google Scholar]
  86. Manor U, Bartholomew S, Golani G, Christenson E, Kozlov M, Higgs H, Spudich J, Lippincott-Schwartz J 2015. A mitochondria-anchored isoform of the actin-nucleating spire protein regulates mitochondrial division. eLife 4:e08828
    [Google Scholar]
  87. Martin M, Hiroyasu A, Guzman RM, Roberts SA, Goodman AG 2018. Analysis of Drosophila STING reveals an evolutionarily conserved antimicrobial function. Cell Rep 23:123537–50.e6
    [Google Scholar]
  88. Matheoud D, Cannon T, Voisin A, Penttinen A-M, Ramet L et al. 2019. Intestinal infection triggers Parkinson's disease-like symptoms in Pink1−/− mice. Nature 571:7766565–69Reported that PINK1/ mice are sensitive to gut infection, leading to development of parkinsonian pathology.
    [Google Scholar]
  89. Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K et al. 2010. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J. Cell Biol. 189:2211–21
    [Google Scholar]
  90. McArthur K, Whitehead LW, Heddleston JM, Li L, Padman BS et al. 2018. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science 359:6378eaao6047
    [Google Scholar]
  91. McPhee CK, Baehrecke EH. 2009. Autophagy in Drosophila melanogaster. Biochim.. Biophys. Acta Mol. Cell Res 1793:91452–60
    [Google Scholar]
  92. McWilliams TG, Prescott AR, Allen GFG, Tamjar J, Munson MJ et al. 2016. mito-QC illuminates mitophagy and mitochondrial architecture in vivo. J. Cell Biol. 214:3333–45
    [Google Scholar]
  93. McWilliams TG, Prescott AR, Montava-Garriga L, Ball G, Singh F et al. 2018. Basal mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand. Cell Metab 27:2439–49.e5
    [Google Scholar]
  94. Melber A, Haynes CM. 2018. UPRmt regulation and output: a stress response mediated by mitochondrial-nuclear communication. Cell Res 28:3281–95
    [Google Scholar]
  95. Mishra P, Chan DC. 2016. Metabolic regulation of mitochondrial dynamics. J. Cell Biol. 212:4379–87
    [Google Scholar]
  96. Morais VA, Haddad D, Craessaerts K, De Bock P-J, Swerts J et al. 2014. PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling. Science 344:6180203–7
    [Google Scholar]
  97. Morais VA, Verstreken P, Roethig A, Smet J, Snellinx A et al. 2009. Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Mol. Med. 1:299–111
    [Google Scholar]
  98. Moreno E, Yan M, Basler K 2002. Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily. Curr. Biol. 12:141263–68
    [Google Scholar]
  99. Murley A, Lackner LL, Osman C, West M, Voeltz GK, Walter P, Nunnari J 2013. ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast. eLife 2:e00422
    [Google Scholar]
  100. Narendra DP, Jin SM, Tanaka A, Suen D-F, Gautier CA et al. 2010a. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLOS Biol 8:1e1000298
    [Google Scholar]
  101. Narendra DP, Kane LA, Hauser DN, Fearnley IM, Youle RJ 2010.b. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy 6:81090–106
    [Google Scholar]
  102. Narendra D, Tanaka A, Suen D-F, Youle RJ 2008. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 183:5795–803Demonstrated the role of Parkin in promoting mitophagy of depolarized mitochondria.
    [Google Scholar]
  103. Nargund AM, Pellegrino MW, Fiorese CJ, Baker BM, Haynes CM 2012. Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337:6094587–90
    [Google Scholar]
  104. Neupert W, Brunner M. 2002. The protein import motor of mitochondria. Nat. Rev. Mol. Cell Biol. 3:8555–65
    [Google Scholar]
  105. Nomura J, So A, Tamura M, Busso N 2015. Intracellular ATP decrease mediates NLRP3 inflammasome activation upon nigericin and crystal stimulation. J. Immunol. 195:125718–24
    [Google Scholar]
  106. Novak I, Kirkin V, McEwan DG, Zhang J, Wild P et al. 2010. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11:145–51
    [Google Scholar]
  107. Noyce AJ, Bestwick JP, Silveira-Moriyama L, Hawkes CH, Giovannoni G et al. 2012. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann. Neurol. 72:6893–901
    [Google Scholar]
  108. Nunnari J, Suomalainen A. 2012. Mitochondria: in sickness and in health. Cell 148:61145–59
    [Google Scholar]
  109. Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T et al. 2012. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 485:7397251–55
    [Google Scholar]
  110. Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H et al. 2012. PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat. Commun. 3:1016
    [Google Scholar]
  111. Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S et al. 2010. Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J. Cell Biol. 191:61141–58
    [Google Scholar]
  112. Palikaras K, Lionaki E, Tavernarakis N 2015. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. . Nature 521:7553525–28
    [Google Scholar]
  113. Park J, Lee SB, Lee S, Kim Y, Song S et al. 2006. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. . Nature 441:70971157–61Established that pink1 functions epistatically with parkin; published concurrently with Clark et al. (2006).
    [Google Scholar]
  114. Pellegrino MW, Nargund AM, Kirienko NV, Gillis R, Fiorese CJ, Haynes CM 2014. Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection. Nature 516:7531414–17
    [Google Scholar]
  115. Pickrell AM, Fukui H, Wang X, Pinto M, Moraes CT 2011. The striatum is highly susceptible to mitochondrial oxidative phosphorylation dysfunctions. J. Neurosci. 31:279895–904
    [Google Scholar]
  116. Pogson JH, Ivatt RM, Sanchez-Martinez A, Tufi R, Wilson E et al. 2014. The complex I subunit NDUFA10 selectively rescues Drosophila pink1 mutants through a mechanism independent of mitophagy. PLOS Genet 10:11e1004815
    [Google Scholar]
  117. Poltorak A, He X, Smirnova I, Liu M-Y, Van Huffel C et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:53962085–88
    [Google Scholar]
  118. Poole AC, Thomas RE, Yu S, Vincow ES, Pallanck L 2010. The mitochondrial fusion-promoting factor Mitofusin is a substrate of the PINK1/Parkin pathway. PLOS ONE 5:4e10054
    [Google Scholar]
  119. Puri R, Cheng X-T, Lin M-Y, Huang N, Sheng Z-H 2019. Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts. Nat. Commun. 10:3645
    [Google Scholar]
  120. Quirós PM, Prado MA, Zamboni N, D'Amico D, Williams RW et al. 2017. Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. J. Cell Biol. 216:72027–45
    [Google Scholar]
  121. Raetz CRH, Whitfield C. 2002. Lipopolysaccharide endotoxins. Annu. Rev. Biochem. 71:635–700
    [Google Scholar]
  122. Reczek CR, Chandel NS. 2015. ROS-dependent signal transduction. Curr. Opin. Cell Biol. 33:8–13
    [Google Scholar]
  123. Rikka S, Quinsay MN, Thomas RL, Kubli DA, Zhang X et al. 2011. Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover. Cell Death Differ 18:4721–31
    [Google Scholar]
  124. Riparbelli MG, Callaini G. 2007. The Drosophila parkin homologue is required for normal mitochondrial dynamics during spermiogenesis. Dev. Biol. 303:1108–20
    [Google Scholar]
  125. Ritchie C, Cordova AF, Hess GT, Bassik MC, Li L 2019. SLC19A1 is an importer of the immunotransmitter cGAMP. Mol. Cell 75:2372–81.e5
    [Google Scholar]
  126. Rodolfo C, Campello S, Cecconi F 2018. Mitophagy in neurodegenerative diseases. Neurochem. Int. 117:156–66
    [Google Scholar]
  127. Samstag CL, Hoekstra JG, Huang C-H, Chaisson MJ, Youle RJ et al. 2018. Deleterious mitochondrial DNA point mutations are overrepresented in Drosophila expressing a proofreading-defective DNA polymerase γ. PLOS Genet 14:11e1007805
    [Google Scholar]
  128. Sánchez-Aparicio MT, Ayllón J, Leo-Macias A, Wolff T, García-Sastre A 2017. Subcellular localizations of RIG-I, TRIM25, and MAVS complexes. J. Virol. 91:2e01155–16
    [Google Scholar]
  129. Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL et al. 2013. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 496:7445372–76
    [Google Scholar]
  130. Schiavi A, Maglioni S, Palikaras K, Shaik A, Strappazzon F et al. 2015. Iron-starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. Curr. . Biol 25:141810–22
    [Google Scholar]
  131. Schindler C, Levy DE, Decker T 2007. JAK-STAT signaling: from interferons to cytokines. J. Biol. Chem. 282:2820059–63
    [Google Scholar]
  132. Seth RB, Sun L, Ea CK, Chen ZJ 2005. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF3. Cell 122:5669–82
    [Google Scholar]
  133. Shi R, Guberman M, Kirshenbaum LA 2018. Mitochondrial quality control: the role of mitophagy in aging. Trends Cardiovasc. Med. 28:4246–60
    [Google Scholar]
  134. Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N et al. 2012. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36:3401–14
    [Google Scholar]
  135. Shukla AK, Spurrier J, Kuzina I, Giniger E 2019. Hyperactive innate immunity causes degeneration of dopamine neurons upon altering activity of Cdk5. Cell Rep 26:1131–44.e4
    [Google Scholar]
  136. Sliter DA, Martinez J, Hao L, Chen X, Sun N et al. 2018. Parkin and PINK1 mitigate STING-induced inflammation. Nature 561:7722258–62Showed that PINK1/Parkin suppresses STING-dependent inflammation; loss of STING alleviated neurodegeneration in Parkin-knockout, PolGmutator mice.
    [Google Scholar]
  137. Steger M, Tonelli F, Ito G, Davies P, Trost M et al. 2016. Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases. eLife 5:e12813
    [Google Scholar]
  138. Sun L, Wu J, Du F, Chen X, Chen ZJ 2013. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339:6121786–91
    [Google Scholar]
  139. Sun N, Yun J, Liu J, Malide D, Liu C et al. 2015. Measuring in vivo mitophagy. Mol. Cell 60:4685–96
    [Google Scholar]
  140. Sun Y, Vashisht AA, Tchieu J, Wohlschlegel JA, Dreier L 2012. Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy. J. Biol. Chem. 287:4840652–60
    [Google Scholar]
  141. Tait SWG, Green DR. 2013. Mitochondrial regulation of cell death. Cold Spring Harb. Perspect. Biol. 5:9a008706
    [Google Scholar]
  142. Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H et al. 1999. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11:4443–51
    [Google Scholar]
  143. Tanaka A, Cleland MM, Xu S, Narendra DP, Suen D-F et al. 2010. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J. Cell Biol. 191:71367–80
    [Google Scholar]
  144. Tieu Q, Okreglak V, Naylor K, Nunnari J 2002. The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission. J. Cell Biol. 158:3445–52
    [Google Scholar]
  145. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT et al. 2004. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429:6990417–23
    [Google Scholar]
  146. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MMK, Harvey K et al. 2004. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. . Science 304:56741158–60First report linking PINK1 mutations with early-onset recessive Parkinson's disease.
    [Google Scholar]
  147. Van Eldik LJ, Carrillo MC, Cole PE, Feuerbach D, Greenberg BD et al. 2016. The roles of inflammation and immune mechanisms in Alzheimer's disease. Alzheimer's Dement. Transl. Res. Clin. Interv. 2:299–109
    [Google Scholar]
  148. Vincow ES, Merrihew G, Thomas RE, Shulman NJ, Beyer RP et al. 2013. The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. PNAS 110:166400–5
    [Google Scholar]
  149. Voigt A, Berlemann LA, Winklhofer KF 2016. The mitochondrial kinase PINK1: functions beyond mitophagy. J. Neurochem. 139:S1232–39
    [Google Scholar]
  150. Walter P, Ron D. 2011. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:60591081–86
    [Google Scholar]
  151. Wang C. 2020. A sensitive and quantitative mKeima assay for mitophagy via FACS. Curr. Protoc. Cell Biol. 86:1e99
    [Google Scholar]
  152. Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL et al. 2011. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147:4893–906
    [Google Scholar]
  153. Weidberg H, Amon A. 2018. MitoCPR—a surveillance pathway that protects mitochondria in response to protein import stress. Science 360:6385eaan4146
    [Google Scholar]
  154. Weinberg SE, Sena LA, Chandel NS 2015. Mitochondria in the regulation of innate and adaptive immunity. Immunity 42:3406–17
    [Google Scholar]
  155. West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM et al. 2015. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520:7548553–57Established that mitochondrial DNA can activate DNA-sensing innate antiviral pathways.
    [Google Scholar]
  156. West AP, Shadel GS. 2017. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat. Rev. Immunol. 17:6363–75
    [Google Scholar]
  157. Whitworth AJ, Pallanck LJ. 2017. PINK1/Parkin mitophagy and neurodegeneration—what do we really know in vivo. Curr. Opin. Genet. Dev. 44:47–53
    [Google Scholar]
  158. Whitworth AJ, Theodore DA, Greene JC, Beneš H, Wes PD, Pallanck LJ 2005. Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease. PNAS 102:228024–29
    [Google Scholar]
  159. Wiedemann N, Pfanner N. 2017. Mitochondrial machineries for protein import and assembly. Annu. Rev. Biochem. 86:685–714
    [Google Scholar]
  160. Wong YC, Holzbaur ELF. 2014. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. PNAS 111:42E4439–48
    [Google Scholar]
  161. Wrobel L, Topf U, Bragoszewski P, Wiese S, Sztolsztener ME et al. 2015. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature 524:7566485–88
    [Google Scholar]
  162. Yamano K, Youle RJ. 2013. PINK1 is degraded through the N-end rule pathway. Autophagy 9:111758–69
    [Google Scholar]
  163. Yamashita SI, Jin X, Furukawa K, Hamasaki M, Nezu A et al. 2016. Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy. J. Cell Biol. 215:5649–65
    [Google Scholar]
  164. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM et al. 1997. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275:53031129–32
    [Google Scholar]
  165. Yaron JR, Gangaraju S, Rao MY, Kong X, Zhang L et al. 2015. K+ regulates Ca2+ to drive inflammasome signaling: dynamic visualization of ion flux in live cells. Cell Death Dis 6:10e1954
    [Google Scholar]
  166. Yoneda M, Miyatake T, Attardi G 1994. Complementation of mutant and wild-type human mitochondrial DNAs coexisting since the mutation event and lack of complementation of DNAs introduced separately into a cell within distinct organelles. Mol. Cell Biol. 14:42699–712
    [Google Scholar]
  167. Yoshii SR, Kishi C, Ishihara N, Mizushima N 2011. Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane. J. Biol. Chem. 286:2219630–40
    [Google Scholar]
  168. Yoshii SR, Mizushima N. 2015. Autophagy machinery in the context of mammalian mitophagy. Biochim. Biophys. Acta Mol. Cell Res. 1853:102797–801
    [Google Scholar]
  169. Youle RJ. 2019. Mitochondria—striking a balance between host and endosymbiont. Science 365:64549855
    [Google Scholar]
  170. Yun J, Puri R, Yang H, Lizzio MA, Wu C et al. 2014. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. eLife 3:e01958
    [Google Scholar]
  171. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T et al. 2010. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:7285104–7
    [Google Scholar]
  172. Zhang Y, Wang ZH, Liu Y, Chen Y, Sun N et al. 2019. PINK1 inhibits local protein synthesis to limit transmission of deleterious mitochondrial DNA mutations. Mol. Cell 73:61127–37.e5
    [Google Scholar]
  173. Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ 2002. A mitochondrial specific stress response in mammalian cells. EMBO J 21:174411–19
    [Google Scholar]
  174. Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S et al. 2018. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560:7717198–203
    [Google Scholar]
  175. Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S et al. 2016. NF-κB restricts inflammasome activation via elimination of damaged mitochondria. Cell 164:5896–910Reported that biomolecules released during mitochondrial stress, such as mitochondrial DNA, can activate the NLRP3 inflammasome.
    [Google Scholar]
  176. Ziviani E, Tao RN, Whitworth AJ 2010. Drosophila Parkin requires Pink1 for mitochondrial translocation and ubiquitinates Mitofusin. PNAS 107:115018–23
    [Google Scholar]
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