Author: ["Atsuko Nakai","Osamu Yamaguchi","Toshihiro Takeda","Yoshiharu Higuchi","Shungo Hikoso","Masayuki Taniike","Shigemiki Omiya","Isamu Mizote","Yasushi Matsumura","Michio Asahi","Kazuhiko Nishida","Masatsugu Hori","Noboru Mizushima","Kinya Otsu"]
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Abstract
Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism in starving cells1,2. Although altered autophagy has been observed in various heart diseases, including cardiac hypertrophy3,4 and heart failure5,6, it remains unclear whether autophagy plays a beneficial or detrimental role in the heart. Here, we report that the cardiac-specific loss of autophagy causes cardiomyopathy in mice. In adult mice, temporally controlled cardiac-specific deficiency of Atg5 (autophagy-related 5), a protein required for autophagy, led to cardiac hypertrophy, left ventricular dilatation and contractile dysfunction, accompanied by increased levels of ubiquitination. Furthermore, Atg5-deficient hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation. On the other hand, cardiac-specific deficiency of Atg5 early in cardiogenesis showed no such cardiac phenotypes under baseline conditions, but developed cardiac dysfunction and left ventricular dilatation one week after treatment with pressure overload. These results indicate that constitutive autophagy in the heart under baseline conditions is a homeostatic mechanism for maintaining cardiomyocyte size and global cardiac structure and function, and that upregulation of autophagy in failing hearts is an adaptive response for protecting cells from hemodynamic stress.Cite this article
Nakai, A., Yamaguchi, O., Takeda, T. et al. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13, 619–624 (2007). https://doi.org/10.1038/nm1574 