Mitophagy and Heart Failure

Overview

Journal J Mol Med (Berl)

Specialty General Medicine

Date 2015 Jan 23

PMID 25609139

Citations 61

Authors

Sarah E Shires

Asa B Gustafsson

Affiliations

Soon will be listed here.

Abstract

Cardiac mitochondria are responsible for generating energy in the form of ATP through oxidative phosphorylation and are crucial for cardiac function. Mitochondrial dysfunction is a major contributor to loss of myocytes and development of heart failure. Myocytes have quality control mechanisms in place to ensure a network of functional mitochondria. Damaged mitochondria are degraded by a process called mitochondrial autophagy, or mitophagy, where the organelle is engulfed by an autophagosome and subsequently delivered to a lysosome for degradation. Evidence suggests that mitophagy is important for cellular homeostasis, and reduced mitophagy leads to inadequate removal of dysfunctional mitochondria. In this review, we discuss the regulation of mitophagy and the emerging evidence of the cardioprotective role of mitophagy. We also address the prospect of therapeutically targeting mitophagy to treat patients with cardiovascular disease.

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References

Dorn 2nd G . Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors. J Cardiovasc Transl Res. 2010; 3(4):374-83. PMC: 2900478. DOI: 10.1007/s12265-010-9174-x. View

Hoshino A, Mita Y, Okawa Y, Ariyoshi M, Iwai-Kanai E, Ueyama T . Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart. Nat Commun. 2013; 4:2308. DOI: 10.1038/ncomms3308. View

Goldberg A . Protein degradation and protection against misfolded or damaged proteins. Nature. 2003; 426(6968):895-9. DOI: 10.1038/nature02263. View

Hamacher-Brady A, Brady N, Gottlieb R . Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J Biol Chem. 2006; 281(40):29776-87. DOI: 10.1074/jbc.M603783200. View

Gomes L, Scorrano L . High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy. Biochim Biophys Acta. 2008; 1777(7-8):860-6. DOI: 10.1016/j.bbabio.2008.05.442. View

Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M . Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014; 510(7503):162-6. DOI: 10.1038/nature13392. View

Kuma A, Mizushima N, Ishihara N, Ohsumi Y . Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J Biol Chem. 2002; 277(21):18619-25. DOI: 10.1074/jbc.M111889200. View

Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T . Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature. 2000; 406(6798):906-10. DOI: 10.1038/35022604. View

Kanamori H, Takemura G, Goto K, Maruyama R, Ono K, Nagao K . Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion. Am J Physiol Heart Circ Physiol. 2011; 300(6):H2261-71. DOI: 10.1152/ajpheart.01056.2010. View

10.

McCray B, Taylor J . The role of autophagy in age-related neurodegeneration. Neurosignals. 2007; 16(1):75-84. DOI: 10.1159/000109761. View

11.

Jaber N, Zong W . Class III PI3K Vps34: essential roles in autophagy, endocytosis, and heart and liver function. Ann N Y Acad Sci. 2013; 1280:48-51. PMC: 6686116. DOI: 10.1111/nyas.12026. View

12.

Hoyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T . Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2. Mol Cell. 2007; 25(2):193-205. DOI: 10.1016/j.molcel.2006.12.009. View

13.

Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T . 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. 2007; 100(6):914-22. DOI: 10.1161/01.RES.0000261924.76669.36. View

14.

Iwata J, Ezaki J, Komatsu M, Yokota S, Ueno T, Tanida I . Excess peroxisomes are degraded by autophagic machinery in mammals. J Biol Chem. 2005; 281(7):4035-41. DOI: 10.1074/jbc.M512283200. View

15.

Houtkooper R, Vaz F . Cardiolipin, the heart of mitochondrial metabolism. Cell Mol Life Sci. 2008; 65(16):2493-506. PMC: 11131844. DOI: 10.1007/s00018-008-8030-5. View

16.

Pankiv S, Clausen T, Lamark T, Brech A, Bruun J, Outzen H . p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007; 282(33):24131-45. DOI: 10.1074/jbc.M702824200. View

17.

Watanabe T, Takemura G, Kanamori H, Goto K, Tsujimoto A, Okada H . Restriction of food intake prevents postinfarction heart failure by enhancing autophagy in the surviving cardiomyocytes. Am J Pathol. 2014; 184(5):1384-94. DOI: 10.1016/j.ajpath.2014.01.011. View

18.

Bhandari P, Song M, Chen Y, Burelle Y, Dorn 2nd G . Mitochondrial contagion induced by Parkin deficiency in Drosophila hearts and its containment by suppressing mitofusin. Circ Res. 2013; 114(2):257-65. PMC: 4392818. DOI: 10.1161/CIRCRESAHA.114.302734. View

19.

Chen Y, Dorn 2nd G . PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science. 2013; 340(6131):471-5. PMC: 3774525. DOI: 10.1126/science.1231031. View

20.

Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H, Tani N . PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat Commun. 2012; 3:1016. PMC: 3432468. DOI: 10.1038/ncomms2016. View