Fig. 4

The mechanism of mitophagy under normal and abnormal physiological conditions. Under normal conditions, PINK1-mediated mitochondrial targeting and degradation inhibit parkin recruitment, thus preventing mitophagy initiation. In contrast, within damaged muscle mitochondria, PINK1 accumulation on the outer membrane triggers parkin recruitment and activation, initiating mitophagy. This cascade involves PINK1 accumulation, dimerization, and phosphorylation, which are crucial for parkin recruitment. Upon recruitment, PINK1 phosphorylates parkin at Ser65, activating it and promoting subsequent ubiquitin release