Mitophagy and heart failure

Journal of Molecular Medicine

Volumn 93, Issue 3, 2015, Pages 253-262

  Shires, Sarah E ^a   Gustafsson, Åsa B ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

Autophagy; Heart failure; Mitochondria; Mitophagy

Indexed keywords

ADAPTOR PROTEIN; ADENYLATE KINASE; BECLIN 1; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE KINASE; CARDIOLIPIN; MITOFUSIN 2; PARKIN; PROTEIN BNIP3; PROTEIN P62; CARDIOTONIC AGENT;

APOPTOSIS; AUTOPHAGOSOME; AUTOPHAGY; CALCIUM SIGNALING; CALCIUM TRANSPORT; CARDIOMYOPATHY; CARDIOVASCULAR DISEASE; HEART FAILURE; HEART INFARCTION; HEART MITOCHONDRION; HEART MUSCLE CELL; HEART MUSCLE CONTRACTILITY; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HEART VENTRICLE HYPERTROPHY; HUMAN; MACROAUTOPHAGY; MITOCHONDRIAL DYNAMICS; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOPHAGY; NONHUMAN; REVIEW; UBIQUITINATION; ANIMAL; DRUG EFFECTS; METABOLISM; PATHOLOGY;

ANIMALS; CALCIUM SIGNALING; CARDIOTONIC AGENTS; HEART FAILURE; HUMANS; MITOCHONDRIA, HEART; MITOCHONDRIAL DEGRADATION;

EID: 84925496485     PISSN: 09462716     EISSN: 14321440     Source Type: Journal    
DOI: 10.1007/s00109-015-1254-6     Document Type: Review

References (97)

1. Baines CP (2010) The cardiac mitochondrion: nexus of stress. Annu Rev Physiol 72:61–80
2. Dai DF, Chen T, Wanagat J, Laflamme M, Marcinek DJ, Emond MJ, Ngo CP, Prolla TA, Rabinovitch PS (2010) Age-dependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria. Aging Cell 9:536–544
3. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA et al (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481–484
4. Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426:895–899
5. Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, Omiya S, Mizote I, Matsumura Y, Asahi M et al (2007) The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13:619–624
6. Hoshino A, Mita Y, Okawa Y, Ariyoshi M, Iwai-Kanai E, Ueyama T, Ikeda K, Ogata T, Matoba S (2013) Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart. Nat Commun 4:2308
7. Billia F, Hauck L, Konecny F, Rao V, Shen J, Mak TW (2011) PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function. Proc Natl Acad Sci U S A 108:9572–9577
8. Kubli DA, Zhang X, Lee Y, Hanna RA, Quinsay MN, Nguyen CK, Jimenez R, Petrosyan S, Murphy AN, Gustafsson AB (2013) Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J Biol Chem 288:915–926
9. Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T, Levine B, Sadoshima J (2007) Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res 100:914–922
10. Hamacher-Brady A, Brady NR, Gottlieb RA (2006) Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J Biol Chem 281:29776–29787
11. Kanamori H, Takemura G, Maruyama R, Goto K, Tsujimoto A, Ogino A, Li L, Kawamura I, Takeyama T, Kawaguchi T et al (2009) Functional significance and morphological characterization of starvation-induced autophagy in the adult heart. Am J Pathol 174:1705–1714
12. Cuervo AM (2008) Autophagy and aging: keeping that old broom working. Trends Genet 24:604–612
13. Yang Z, Klionsky DJ (2010) Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 22:124–131
14. Zeng X, Overmeyer JH, Maltese WA (2006) Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. J Cell Sci 119:259–270
15. Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T (2004) LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci 117:2805–2812
16. Kuma A, Mizushima N, Ishihara N, Ohsumi Y (2002) Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J Biol Chem 277:18619–18625
17. Lamark T, Kirkin V, Dikic I, Johansen T (2009) NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets. Cell Cycle 8:1986–1990
18. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282:24131–24145
19. Jaber N, Zong WX (2013) Class III PI3K Vps34: essential roles in autophagy, endocytosis, and heart and liver function. Ann N Y Acad Sci 1280:48–51
20. Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T, Mora M, Riggs JE, Oh SJ, Koga Y et al (2000) Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 406:906–910
21. Tanaka Y, Guhde G, Suter A, Eskelinen EL, Hartmann D, Lullmann-Rauch R, Janssen PM, Blanz J, von Figura K, Saftig P (2000) Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature 406:902–906
22. Stypmann J, Glaser K, Roth W, Tobin DJ, Petermann I, Matthias R, Monnig G, Haverkamp W, Breithardt G, Schmahl W et al (2002) Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L. Proc Natl Acad Sci U S A 99:6234–6239
23. He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q et al (2012) Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 481:511–515
24. Kanamori H, Takemura G, Goto K, Maruyama R, Ono K, Nagao K, Tsujimoto A, Ogino A, Takeyama T, Kawaguchi T et al (2011) Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion. Am J Physiol Heart Circ Physiol 300:H2261–2271
25. Watanabe T, Takemura G, Kanamori H, Goto K, Tsujimoto A, Okada H, Kawamura I, Ogino A, Takeyama T, Kawaguchi T et al (2014) Restriction of food intake prevents postinfarction heart failure by enhancing autophagy in the surviving cardiomyocytes. Am J Pathol 184:1384–1394
26. Bhuiyan MS, Pattison JS, Osinska H, James J, Gulick J, McLendon PM, Hill JA, Sadoshima J, Robbins J (2013) Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest 123:5284–5297
27. Zhu H, Tannous P, Johnstone JL, Kong Y, Shelton JM, Richardson JA, Le V, Levine B, Rothermel BA, Hill JA (2007) Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest 117:1782–1793
28. Tannous P, Zhu H, Nemchenko A, Berry JM, Johnstone JL, Shelton JM, Miller FJ Jr, Rothermel BA, Hill JA (2008) Intracellular protein aggregation is a proximal trigger of cardiomyocyte autophagy. Circulation 117:3070–3078
29. Iwata J, Ezaki J, Komatsu M, Yokota S, Ueno T, Tanida I, Chiba T, Tanaka K, Kominami E (2006) Excess peroxisomes are degraded by autophagic machinery in mammals. J Biol Chem 281:4035–4041
30. Bernales S, Schuck S, Walter P (2007) ER-phagy: selective autophagy of the endoplasmic reticulum. Autophagy 3:285–287
31. Elmore SP, Qian T, Grissom SF, Lemasters JJ (2001) The mitochondrial permeability transition initiates autophagy in rat hepatocytes. FASEB J 15:2286–2287
32. Lazarou M, Jin SM, Kane LA, Youle RJ (2012) Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev Cell 22:320–333
33. Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 191:933–942
34. Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803
35. Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ (2014) PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 205:143–153
36. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T et al (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510:162–166
37. Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H, Tani N, Kimura M, Go E, Koyano F, Funayama M et al (2012) PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat Commun 3:1016
38. Chen Y, Dorn GW 2nd (2013) PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340:471–475
39. Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS, Hofmann K, Alessi DR, Knebel A, Trost M, Muqit MM (2014) Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J 460:127–139
40. Okatsu K, Iemura S, Koyano F, Go E, Kimura M, Natsume T, Tanaka K, Matsuda N (2012) Mitochondrial hexokinase HKI is a novel substrate of the Parkin ubiquitin ligase. Biochem Biophys Res Commun 428:197–202
41. Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12:119–131
42. Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ (2010) Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 191:1367–1380
43. Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL (2011) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147:893–906
44. Kirkin V, Lamark T, Sou YS, Bjorkoy G, Nunn JL, Bruun JA, Shvets E, McEwan DG, Clausen TH, Wild P et al (2009) A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell 33:505–516
45. Gomes LC, Scorrano L (2008) High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy. Biochim Biophys Acta 1777:860–866
46. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G et al (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27:433–446
47. Hanna RA, Quinsay MN, Orogo AM, Giang K, Rikka S, Gustafsson AB (2012) 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
48. Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Lohr F, Popovic D, Occhipinti A et al (2010) Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11:45–51
49. Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W et al (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14:177–185
50. Houtkooper RH, Vaz FM (2008) Cardiolipin, the heart of mitochondrial metabolism. Cell Mol Life Sci 65:2493–2506
51. Chu CT, Ji J, Dagda RK, Jiang JF, Tyurina YY, Kapralov AA, Tyurin VA, Yanamala N, Shrivastava IH, Mohammadyani D et al (2013) Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat Cell Biol 15:1197–1205
52. Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454:232–235
53. Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J, Mazure NM (2009) Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29:2570–2581
54. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939
55. Glick D, Zhang W, Beaton M, Marsboom G, Gruber M, Simon MC, Hart J, Dorn GW 2nd, Brady MJ, Macleod KF (2012) BNip3 regulates mitochondrial function and lipid metabolism in the liver. Mol Cell Biol 32:2570–2584
56. Chen G, Han Z, Feng D, Chen Y, Chen L, Wu H, Huang L, Zhou C, Cai X, Fu C et al (2014) A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy. Mol Cell 54:362–377
57. Lee Y, Lee HY, Hanna RA, Gustafsson AB (2011) Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes. Am J Physiol Heart Circ Physiol 301:H1924–1931
58. Ding WX, Ni HM, Li M, Liao Y, Chen X, Stolz DB, Dorn GW 2nd, Yin XM (2010) 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
59. Wu W, Tian W, Hu Z, Chen G, Huang L, Li W, Zhang X, Xue P, Zhou C, Liu L et al (2014) ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep 15:566–575
60. Tracy K, Dibling BC, Spike BT, Knabb JR, Schumacker P, Macleod KF (2007) BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy. Mol Cell Biol 27:6229–6242
61. Chan DC (2012) Fusion and fission: interlinked processes critical for mitochondrial health. Annu Rev Genet 46:265–287
62. Gomes LC, di Benedetto G, Scorrano L (2011) During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol 13:589–598
63. Bhandari P, Song M, Chen Y, Burelle Y, Dorn GW 2nd (2014) Mitochondrial contagion induced by Parkin deficiency in Drosophila hearts and its containment by suppressing mitofusin. Circ Res 114:257–265
64. Ikeda Y, Shirakabe A, Maejima Y, Zhai P, Sciarretta S, Toli J, Nomura M, Mihara K, Egashira K, Ohishi M et al (2014) Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress. Circ Res. doi:10.1161/CIRCRESAHA.116.303356
65. Hardie DG (2011) AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev 25:1895–1908
66. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL et al (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476:341–345
67. de Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:336–340
68. Mallilankaraman K, Cardenas C, Doonan PJ, Chandramoorthy HC, Irrinki KM, Golenar T, Csordas G, Madireddi P, Yang J, Muller M et al (2012) MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism. Nat Cell Biol 14:1336–1343
69. Perocchi F, Gohil VM, Girgis HS, Bao XR, McCombs JE, Palmer AE, Mootha VK (2010) MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature 467:291–296
70. Cardenas C, Miller RA, Smith I, Bui T, Molgo J, Muller M, Vais H, Cheung KH, Yang J, Parker I et al (2010) Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria. Cell 142:270–283
71. Balaban RS (2009) Domestication of the cardiac mitochondrion for energy conversion. J Mol Cell Cardiol 46:832–841
72. Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J, Edelman AM, Frenguelli BG, Hardie DG (2005) Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2:9–19
73. Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR, Carlson M, Carling D (2005) Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2:21–33
74. Hoyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, Bianchi K, Fehrenbacher N, Elling F, Rizzuto R et al (2007) Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2. Mol Cell 25:193–205
75. Carreira RS, Lee Y, Ghochani M, Gustafsson AB, Gottlieb RA (2010) Cyclophilin D is required for mitochondrial removal by autophagy in cardiac cells. Autophagy 6:462–472
76. Cui T, Fan C, Gu L, Gao H, Liu Q, Zhang T, Qi Z, Zhao C, Zhao H, Cai Q et al (2011) Silencing of PINK1 induces mitophagy via mitochondrial permeability transition in dopaminergic MN9D cells. Brain Res 1394:1–13
77. Deas E, Wood NW, Plun-Favreau H (2011) Mitophagy and Parkinson’s disease: the PINK1-parkin link. Biochim Biophys Acta 1813:623–633
78. Kubli DA, Quinsay MN, Gustafsson AB (2013) Parkin deficiency results in accumulation of abnormal mitochondria in aging myocytes. Commun Integr Biol 6:e24511
79. Song M, Chen Y, Gong G, Murphy E, Rabinovitch PS, Dorn GW 2nd (2014) Super-suppression of mitochondrial reactive oxygen species signaling impairs compensatory autophagy in primary mitophagic cardiomyopathy. Circ Res 115:348–353
80. Santel A, Fuller MT (2001) Control of mitochondrial morphology by a human mitofusin. J Cell Sci 114:867–874
81. de Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456:605–610
82. Dorn GW 2nd (2010) Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors. J Cardiovasc Transl Res 3:374–383
83. McCray BA, Taylor JP (2008) The role of autophagy in age-related neurodegeneration. Neuro-Signals 16:75–84
84. Taneike M, Yamaguchi O, Nakai A, Hikoso S, Takeda T, Mizote I, Oka T, Tamai T, Oyabu J, Murakawa T et al (2010) Inhibition of autophagy in the heart induces age-related cardiomyopathy. Autophagy 6:600–606
85. Grivennikova VG, Kareyeva AV, Vinogradov AD (2010) What are the sources of hydrogen peroxide production by heart mitochondria? Biochim Biophys Acta 1797:939–944
86. Sohal RS, Ku HH, Agarwal S, Forster MJ, Lal H (1994) Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 74:121–133
87. Wong ES, Tan JM, Wang C, Zhang Z, Tay SP, Zaiden N, Ko HS, Dawson VL, Dawson TM, Lim KL (2007) Relative sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterations. J Biol Chem 282:12310–12318
88. Winklhofer KF, Henn IH, Kay-Jackson PC, Heller U, Tatzelt J (2003) Inactivation of parkin by oxidative stress and C-terminal truncations: a protective role of molecular chaperones. J Biol Chem 278:47199–47208
89. Tan JM, Wong ES, Lim KL (2009) Protein misfolding and aggregation in Parkinson’s disease. Antioxid Redox Signal 11:2119–2134
90. Siddall HK, Yellon DM, Ong SB, Mukherjee UA, Burke N, Hall AR, Angelova PR, Ludtmann MH, Deas E, Davidson SM et al (2013) Loss of PINK1 increases the heart’s vulnerability to ischemia-reperfusion injury. PLoS One 8:e62400
91. Zhou S, Starkov A, Froberg MK, Leino RL, Wallace KB (2001) Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin. Cancer Res 61:771–777
92. Diwan A, Wansapura J, Syed FM, Matkovich SJ, Lorenz JN, Dorn GW 2nd (2008) Nix-mediated apoptosis links myocardial fibrosis, cardiac remodeling, and hypertrophy decompensation. Circulation 117:396–404
93. Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, Koesters AG, Li H, Kirshenbaum LA, Hahn HS, Robbins J et al (2007) Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. J Clin Invest 117:2825–2833
94. Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M, Kirshenbaum LA, Gottlieb RA, Gustafsson AB (2007) Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ 14:146–157
95. Yussman MG, Toyokawa T, Odley A, Lynch RA, Wu G, Colbert MC, Aronow BJ, Lorenz JN, Dorn GW 2nd (2002) Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers apoptotic cardiomyopathy. Nat Med 8:725–730
96. Zesiewicz TA, Strom JA, Borenstein AR, Hauser RA, Cimino CR, Fontanet HL, Cintron GB, Staffetti JF, Dunne PB, Sullivan KL (2004) Heart failure in Parkinson’s disease: analysis of the United States medicare current beneficiary survey. Parkinsonism Relat Disord 10:417–420
97. Rana A, Rera M, Walker DW (2013) Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan. Proc Natl Acad Sci U S A 110:8638–8643