Figure 2. Parkin-dependent and – independent mechanisms of mitophagy.
PINK1 stabilization initiates both pathways. Upper: phosphorylation of Mfn2 recruits cytosolic Parkin, and of ubiquitin activates Parkin, provoking ubiquitination of outer mitochondrial membrane proteins that attract atuophagosomal LC3 via docking protein p62. Lower: phosphorylation of ubiquitinated membrane proteins attracts autophagosomal LC3 via autophagy receptors optineurin (OPTN) or nuclear dot protein 52 (NDP52). The relative roles of each pathway in hearts and elsewhere are unknown.