Is autophagy a double-edged sword for the heart?

被引:54
作者
Gurusamy, N. [1 ]
Das, D. K. [1 ]
机构
[1] Univ Connecticut, Cardiovasc Res Ctr, Sch Med, Farmington, CT 06030 USA
关键词
autophagy; myocardium; heart disease; oxidative stress; Atg gene; autophagosome; CHAPERONE-MEDIATED AUTOPHAGY; HUMAN HIBERNATING MYOCARDIUM; UBIQUITIN-PROTEASOME SYSTEM; ACTIVATED PROTEIN-KINASE; CELL-DEATH; OXIDATIVE STRESS; ISCHEMIA/REPERFUSION INJURY; CONJUGATION SYSTEM; 3-KINASE COMPLEX; MACROAUTOPHAGY;
D O I
10.1556/APhysiol.96.2009.3.2
中图分类号
学科分类号
摘要
Autophagy is a catabolic process through which damaged or long-lived proteins, macromolecules and organelles are degraded using lysosomal degradative machinery. Since cardiac myocytes are terminally differentiated, the role of autophagy is essential to maintain the homeostasis of the myocardium. Autophagy supplies nutrients for the synthesis of essential proteins during starvation and thus helps to extend cell survival. Although autophagy is non-selective, under oxidative conditions it effectively removes oxidatively damaged mitochondria, peroxisomes and endoplasmic reticulum. Thus, autophagy can protect the cells from apoptosis and other major injuries, and it is considered to be in the cross-road between cell death and survival. However, excess autophagy can destroy essential cellular components and lead to cell death. The function of autophagy in normal and in the conditions of cardiac diseases such as heart failure, cardiomyopathy, cardiac hypertrophy, and ischemia-reperfusion injury is discussed.
引用
收藏
页码:267 / 276
页数:10
相关论文
共 86 条
[51]   A protein conjugation system essential for autophagy [J].
Mizushima, N ;
Noda, T ;
Yoshimori, T ;
Tanaka, Y ;
Ishii, T ;
George, MD ;
Klionsky, DJ ;
Ohsumi, M ;
Ohsumi, Y .
NATURE, 1998, 395 (6700) :395-398
[52]   Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells [J].
Mizushima, N ;
Yamamoto, A ;
Hatano, M ;
Kobayashi, Y ;
Kabeya, Y ;
Suzuki, K ;
Tokuhisa, T ;
Ohsumi, Y ;
Yoshimori, T .
JOURNAL OF CELL BIOLOGY, 2001, 152 (04) :657-667
[53]   Methods for monitoring autophagy [J].
Mizushima, N .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2004, 36 (12) :2491-2502
[54]   In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker [J].
Mizushima, N ;
Yamamoto, A ;
Matsui, M ;
Yoshimori, T ;
Ohsumi, Y .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (03) :1101-1111
[55]   Autophagosome formation in mammalian cells [J].
Mizushima, N ;
Ohsumi, Y ;
Yoshimori, T .
CELL STRUCTURE AND FUNCTION, 2002, 27 (06) :421-429
[56]  
MORTIMORE GE, 1988, J BIOL CHEM, V263, P2506
[57]   The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress [J].
Nakai, Atsuko ;
Yamaguchi, Osamu ;
Takeda, Toshihiro ;
Higuchi, Yoshiharu ;
Hikoso, Shungo ;
Taniike, Masayuki ;
Omiya, Shigemiki ;
Mizote, Isamu ;
Matsumura, Yasushi ;
Asahi, Michio ;
Nishida, Kazuhiko ;
Hori, Masatsugu ;
Mizushima, Noboru ;
Otsu, Kinya .
NATURE MEDICINE, 2007, 13 (05) :619-624
[58]   Regulation of macroautophagy by mTOR and Beclin 1 complexes [J].
Pattingre, Sophie ;
Espert, Lucile ;
Biard-Piechaczyk, Martine ;
Codogno, Patrice .
BIOCHIMIE, 2008, 90 (02) :313-323
[59]   The ubiquitin-proteasome system in cardiac physiology and pathology [J].
Powell, Saul R. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 291 (01) :H1-H19
[60]   Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease [J].
Ravikumar, B ;
Vacher, C ;
Berger, Z ;
Davies, JE ;
Luo, SQ ;
Oroz, LG ;
Scaravilli, F ;
Easton, DF ;
Duden, R ;
O'Kane, CJ ;
Rubinsztein, DC .
NATURE GENETICS, 2004, 36 (06) :585-595