Top

Published in:

01-01-2010

How does the heart (not) die? The role of autophagy in cardiomyocyte homeostasis and cell death

Authors: Pavittarpaul Dhesi, Faramarz Tehrani, Justin Fuess, Ernst R. Schwarz

Published in: Heart Failure Reviews | Issue 1/2010

Abstract

Autophagy plays a critical and seemingly dual-purposed role in cardiomyocytes, being implicated as a mechanism of both cellular survival, for example, during ischemia/reperfusion injury and a mechanism of cell death at stages in which progressive myocyte alterations are beyond repair. This review aims to highlight the current literature as it relates to autophagy in cardiomyocytes. It provides background into the mechanisms of cell death, discusses the details that are known about the ubiquitin proteasome system and autophagy, delves into the pathways that are known to initiate and inhibit autophagy, and comments on the role of autophagy in cardiomyocyte homeostasis and cell death.

Kunapali S, Rosanio S, Schwarz E (2006) ‘How do cardiomyocytes die?’ Apoptosis and autophagic cell death in cardiac myocytes. J Card Fail 12:381–391. doi:10.1016/j.cardfail.2006.02.002 CrossRef

Majn G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146:3–15

Beau I, Esclatine A, Codogno P (2008) Lost to translation: when autophagy targets mature ribosomes. Trends Cell Biol 18:311–314. doi:10.1016/j.tcb.2008.05.001 CrossRefPubMed

Buja LM, Vela D (2008) Cardiomyocyte death and renewal in the normal and diseased heart. Cardiovasc Pathol 17:349–374. doi:10.1016/j.carpath.2008.02.004 CrossRefPubMed

Wang X, Su H, Ranek M (2008) Protein quality control and degradation in cardiomyocytes. J Mol Cell Cardiol 45:11–27. doi:10.1016/j.yjmcc.2008.03.025 CrossRefPubMed

Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069–1075. doi:10.1038/nature06639 CrossRefPubMed

Abeliovich H (2007) Mitophagy: the life-or-death dichotomy includes Yeast. Autophagy 3:275–277PubMed

Bernales S, Schuck S, Walter P (2007) ER-phagy: selective autophagy of the endoplasmic reticulum. Autophagy 3:285–287PubMed

Kostin S (2003) Myocytes die by multiple mechanisms in failing human hearts. Circ Res 92:715–724. doi:10.1161/01.RES.0000067471.95890.5C CrossRefPubMed

10.

Tanaka Y, Guhde G, Suter A (2000) Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature 406:902–906. doi:10.1038/35022595 CrossRefPubMed

11.

Hickson-Bick D, Jones C, Buja LM (2008) Stimulation of mitochondrial biogenesis and autophagy by lipopolysaccharide in the neonatal rate cardiomyocyte protects against programmed cell death. J Mol Cell Cardiol 44:411–418. doi:10.1016/j.yjmcc.2007.10.013 CrossRefPubMed

12.

Iwai-Kanai E, Yuan H, Huang C, Sayen MR, Perry-Garza CN, Kim L, Gottlieb RA (2008) A method to measure cardiac flux in vivo. Autophagy 4:322–329PubMed

13.

Mizushima N, Yoshimori T (2007) How to interpret LC3 immunoblotting. Autophagy 3:542–545PubMed

14.

Hamacher-Brady A, Brady NR, Gottlieb RA (2006) The interplay between pro-death and pro-survival signaling pathways in myocardial ischemia/reperfusion injury: apoptosis meets autophagy. Cardiovasc Drugs Ther 20:445–462. doi:10.1007/s10557-006-0583-7 CrossRefPubMed

15.

Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double edged sword. Science 306:990–995. doi:10.1126/science.1099993 CrossRefPubMed

16.

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. doi:10.1016/j.cell.2005.07.002 CrossRefPubMed

17.

Nishida K, Kyoi S, Yamaguchi O, Sadoshima J, Otsu K (2008) The role of autophagy in the heart. Autophagy 16:31–38

18.

Tasdemir E, Maiuri MC, Galluzzi L, Vitale I, Djavaheri-Mergny M, D’Amelio M, Criollo A, Morselli E, Zhu C, Harper F, Nannmark U, Samara C, Pinton P, Vicencio JM, Carnuccio R, Moll UM, Madeo F, Paterlini-Brechot P, Rizzuto R, Szabadkai G, Pierron G, Blomgren K, Tavernarakis N, Codogno P, Cecconi F, Kroemer G (2008) Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 6:676–687. doi:10.1038/ncb1730 CrossRef

19.

Tasdemir E, Maiuri MC, Morselli E, Criollo A, D’Amelio M, Djavaheri-Mergny M, Cecconi F, Tavernarkis N, Kroemer G (2008) A dual role of p53 in the control of autophagy. Autophagy 4:810–814PubMed

20.

Brady N, Hamacher-Brady A, Yuan H, Gottlieb R (2007) The autophagic response to nutrient deprivation in the hl-1 cardiac myocyte is modulated by Bcl-2 and sarco/endoplasmic reticulum calcium stores. FEBS J 274:3184–3197. doi:10.1111/j.1742-4658.2007.05849.x CrossRefPubMed

21.

Hammacher-Brady A, Brady N, Logue SE, Sayen MR, Jinno M (2007) Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ 14:146–157. doi:10.1038/sj.cdd.4401936 CrossRef

22.

Hammacher-Brady A, Brady N, Gottlieb R, Gustafsso A (2006) Autophagy as a protective response to Bnip3-mediated apoptotic signaling in the heart. Autophagy 2:307–309

23.

Dosenko V, Nagiban V, Tumanovska L, Moibenko A (2006) Protective effect of autophagy in anoxia-reoxygenation of isolated cardiomyocyte. Autophagy 2:305–306PubMed

24.

Ichimura Y, Kumanomidou T, Sou Y, Mizushima T, Ezaki J, Ueno T, Kominami E, Yamane T, Tanaka K, Komatsu M (2008) Structural basis for sorting mechanism of p62 in selective autophagy. J Biol Chem 283:22847–22857. doi:10.1074/jbc.M802182200 CrossRefPubMed

25.

Saftig P, Geersten W, Eskelinin EL (2008) LAMP-2: a control step for phagosome and autophagosome maturation. Autophagy 4:510–512PubMed

26.

Sarkar S, Davies JE, Huang Z, Tunnacliffe A, Rubinsztein DC (2007) Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alphya-synuclein. J Biol Chem 228:5641–5652

27.

Tannous P, Zhu H, Nemchenko A, Berry J, 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. doi:10.1161/CIRCULATIONAHA.107.763870 CrossRefPubMed

28.

Yan L, Vatner D, Kim SJ, Ge H, Masurekar M, Massover WH, Yang G, Matsui Y, Sadoshima J, Vatner SF (2005) Autophagy in chronically ischemic myocardium. Proc Natl Acad Sci USA 102:13807–13812. doi:10.1073/pnas.0506843102 CrossRefPubMed

29.

Depre C, Vatner S (2007) Cardioprotection in stunned and hibernating myocardium. Heart Fail Rev 12:307–317. doi:10.1007/s10741-007-9040-3 CrossRefPubMed

30.

Yan L, Sandoshima J, Vatner DE, Vatner SF (2006) Autophagy: a novel protective mechanism in chronic ischemia. Cell Cycle (Georgetown, Tex) 5:1175–1177

31.

Lum JJ, De Berardanis RJ, Thompson CB (2005) Autophagy in metazoans: cell survival in the land of the plenty. Nat Rev Mol Cell Biol 6:439–448. doi:10.1038/nrm1660 CrossRefPubMed

32.

Matsui Y, Takagi H, Qu X, Abdellatif M, Sakado 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. doi:10.1161/01.RES.0000261924.76669.36 CrossRefPubMed

33.

Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, Omiya S, Mizote I, Matsumara Y, Asahi M, Nishida K, Hori M, Mizushima N, Otsu K (2007) The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13:619–624. doi:10.1038/nm1574 CrossRefPubMed

34.

Elsasser A, Vogt A, Nef H, Kostin S, Moollmann H, Skwara W, Bode C, Hamm C, Schaper J (2004) Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death. J Am Coll Cardiol 43:2191–2199. doi:10.1016/j.jacc.2004.02.053 CrossRefPubMed

Title: How does the heart (not) die? The role of autophagy in cardiomyocyte homeostasis and cell death
Authors: Pavittarpaul Dhesi
Faramarz Tehrani
Justin Fuess
Ernst R. Schwarz
Publication date: 01-01-2010
Publisher: Springer US
Published in: Heart Failure Reviews / Issue 1/2010
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-009-9137-y

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Keynote webinar | Spotlight on medication adherence

Springer Medicine

How does the heart (not) die? The role of autophagy in cardiomyocyte homeostasis and cell death

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2010

Cell delivery and tracking in post-myocardial infarction cardiac stem cell therapy: an introduction for clinical researchers

Echocardiography in the assessment of left ventricular longitudinal systolic function: current methodology and clinical applications

Why, when, and how to assess pulmonary congestion in heart failure: pathophysiological, clinical, and methodological implications

Architecture of the left ventricle: insights for optimal surgical ventricular restoration

Potential of endothelin-1 and vasopressin antagonists for the treatment of congestive heart failure

Cardiomyopathy in Duchenne muscular dystrophy: pathogenesis and therapeutics

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page