The Progress of Mitophagy and Related Pathogenic Mechanisms of the Neurodegenerative Diseases and Tumor

Figure 3

The components and machinery of the mitophagy [14]. (1) In yeast, three examples of mitophagy are represented: (a) the classic starvation/rapamycin-induced pathway is mediated by TOR and results in macroautophagy. Atg8 interacts with Atg32, which in turn interacts with Atg11 at the PAS and engulfs and delivers the mitochondria to the vacuole. (b) Induced autophagy in the stationary phase. This pathway relies on the autophagosomal identification of mitochondria via the Aup1 and results in macroautophagic disposal; (c) starvation and rapamycin can also induce macroautophagy, a process in which recognition of Uth1 results in the direct engulfment of mitochondria by the vacuole. (2) Two further examples of mitophagy in mammals are represented: (d) MARF, MIF1, and PINK1 localizes on the mitochondrial outer membrane and interacts with Parkin and leads to the polyubiquitination of damaged and/or depolarized mitochondria, which ultimately leads to the macroautophagic engulfment and delivery of the mitochondria to the lysosome for destruction; (e) reticulocytes remove mitochondria through NIX recognition by the mammalian Atg8 homologue, LC3.