Figure 2: Phosphatase and tensin homologue deleted on chromosome 10- (PTEN-) induced putative kinase 1- (PINK1-) Parkin mediated initiation of mitophagy and inhibition of mitochondrial fusion. PINK1 recognizes damaged mitochondria that exhibit mitochondrial dysfunction. As a result, PINK1 accumulates on the outer mitochondrial membrane, which recruits and activates Parkin via its phosphorylation at Ser65 on the N-terminal ubiquitin-like domain and phosphorylates ubiquitin. Phosphorylated Parkin then recruits and forms ubiquitin chains on mitofusin (MFN) located on the outer mitochondrial membrane, leading to its proteasomal degradation and inhibition of mitochondrial fusion. As such, the ubiquitination of MFN promotes mitophagy through the recruitment of autophagy substrates and receptors such as p62, LC3, and Fundc1 that facilitates the elimination of the targeted mitochondria.