Mitochondria play an essential role in oxidative phosphorylation, fatty acid oxidation, and the regulation of apoptosis. However, this organelle also produces reactive oxygen species (ROS) that continually inflict oxidative damage on mitochondrial DNA, proteins, and lipids, which causes further production of ROS. To oppose this oxidative stress, mitochondria possess quality control systems that include antioxidant enzymes and the repair or degradation of damaged mitochondrial DNA and proteins. If the oxidative stress exceeds the capacity of the mitochondrial quality control system, it seems that autophagy degrades the damaged mitochondria to maintain cellular homeostasis. Indeed, recent evidence from yeast to mammals indicates that the autophagy-dependent degradation of mitochondria (mitophagy) contributes to eliminate dysfunctional, aged, or excess mitochondria. In this paper, we describe the molecular processes and regulatory mechanisms of mitophagy in yeast and mammalian cells. 1. Selective Degradation of Mitochondria by Autophagy Autophagy is a catabolic process that degrades cytoplasmic components and organelles and is conserved in almost all eukaryotes. Autophagy is initiated in response to cellular stresses such as nutrient starvation, oxidative stress, infection, or inflammatory stimuli. Upon its induction, a cup-shaped double-membrane structure, called an isolation membrane (or phagophore), emerges in the cytoplasm, then the isolation membrane elongates with curvature and finally becomes enclosed, forming an autophagosome containing cytoplasmic components. Subsequently, autophagosomes fuse with lysosomes/vacuoles, and lysosomal hydrolases degrade the sequestered material [1–5]. This process facilitates physiological processes such as survival during starvation, clearance of dysfunctional or aggregated proteins and organelles, development, differentiation, and aging [6–8]. In addition to the nonselective degradation of cytoplasmic components, autophagy can selectively degrade specific organelles or proteins. These include peroxisomes, endoplasmic reticulum, ribosomes, the nucleus, intracellular pathogens, protein aggregates, lipid droplets, and secretory granules. These catabolic processes are termed pexophagy, reticulophagy (ERphagy), ribophagy, nucleophagy, xenophagy, aggrephagy, lipophagy, and zymophagy, respectively. Similarly, the yeast Cvt complex (a protein complex comprising aminopeptidase I (Ape1) and alpha-mannosidase (Ams1)) is delivered to vacuoles via an autophagy-like process; Ape1 and Ams1 are processed and activated in the
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