Fig. 1.
From: PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol
An overview of PINK1/Parkin-mediated mitophagy. In damaged mitochondria that lose mitochondrial membrane potential (ΔΨm), PINK1 import is blocked, which results in the accumulation of full-length PINK1 on the outer mitochondrial membrane (OMM). The TOM complex ensures the correct positioning of dimeric PINK1, and PINK1 kinase activity becomes activated through auto-phosphorylation. PINK1 phosphorylates ubiquitin, which triggers recruitment of Parkin recruitment to mitochondria and activation of its E3 ligase activity. At the same time, phospho-ubiquitin recruits autophagy receptors to initiate autophagosome formation. Parkin acts as an enhancer of this signaling through further ubiquitination of mitochondrial proteins