Molecular Mechanisms of Mitochondrial Autophagy/Mitophagy in the Heart

Abstract

Mitochondrial quality is a crucial determinant of cell viability, and mitochondrial autophagy plays a central role in this control mechanism. Based on studies in yeast, numerous investigations of this process have been conducted and the framework of mammalian mitochondrial autophagy is progressively appearing. However, many enigmas about the molecular mechanisms involved remain unsolved. Furthermore, the pathological significance of mitochondrial autophagy in the heart remains largely unclear. In this review, we discuss the current understanding of mitochondrial autophagy in mammals with reference to that in yeast. Regarding the process in yeast, some points of uncertainty have arisen. We also summarize recent advances in the research of autophagy and mitochondrial autophagy in the heart. This article is a part of a review series on Autophagy in Health and Disease.

Cardiac-specific overexpression of metallothionein attenuates myocardial remodeling and contractile dysfunction in l-NAME-induced experimental hypertension: Role of autophagy regulation

“…Basal level of autophagy is essential to the cellular physiological function and survival whereas excessive autophagy may promote autophagic cell death (Hara et al, 2006;Komatsu et al, 2006;Ren and Taegtmeyer, 2015). Dysregulated autophagy has been demonstrated to contribute to the pathogenesis of atherosclerosis, ischemia/reperfusion injury, cardiomyopathy, diabetes mellitus, and hypertension (Ren and Taegtmeyer, 2015;Saito and Sadoshima, 2015). In addition, autophagy is known to participate in the pathogenesis of pressure overload-induced heart diseases (Martinet et al, 2007;Shen et al, 2015;Won Suk Jahng et al, 2015;Xu et al, 2014).…”

Aging and Autophagy in the Heart

“…Autophagosomes containing only mitochondria have been observed in electron microscopic analyses of the hearts of adult mice, providing evidence for the existence of mitophagy in the heart 126 . The molecular mechanisms mediating mitochondrial autophagy and its functional significance in the heart have been reviewed recently 127 . In perhaps the most well-characterized mechanism of mitochondrial autophagy, depolarized mitochondria are marked by a PINK1-Parkin-Mfn2-dependent mechanism and engulfed by autophagosomes through an LC3-receptor-dependent mechanism 128 .…”

Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload–Induced Mitochondrial Dysfunction and Heart Failure

“…For example, activation of a series of events, including stabilization of Pink1 on depolarized mitochondria, phosphorylation of Mfn2, recruitment of Parkin to mitochondria, and recognition of depolarized mitochondria by autophagosomes, specifically eliminates damaged mitochondria; this process is termed mitochondrial autophagy or mitophagy 4, 5 . Mitochondria are the primary source of cellular ATP, but when they malfunction, they become a major source of oxidative stress and trigger both apoptosis and necrosis.…”