Autophagy machinery in the context of mammalian mitophagy.

Autophagy is an intracellular catabolic system that degrades cytoplasmic proteins and organelles. Damaged mitochondria can be degraded by a selective type of autophagy, which is termed mitophagy. PINK1-Parkin-dependent mitophagy has been extensively studied in the mammalian system. PINK1 accumulates on damaged mitochondria to recruit Parkin, which subsequently ubiquitinates a broad range of outer mitochondrial membrane proteins. Ubiquitinated mitochondria associate with the autophagosome formation site, and are selectively incorporated into autophagosomes. During this process, damaged mitochondria first associate with the autophagosome formation site together with upstream autophagy factors, then are efficiently incorporated into autophagosomes through binding with autophagosome adaptors. This "two-step model" may be applied to other selective types of autophagy.