Fig. 2.

Schematic representation of mitochondrial fission and mitophagy. Mitophagy is preceded by mitochondrial division, which generates individual mitochondrial fragments of feasible size for encapsulation. Upon malfunctioning of a mitochondrion, it suffers a depolarization, which interrupts normal proteolytic processing of PINK1, leading to PINK1 accumulation in the mitochondrion and phosporylation of its targets, which include ubiquitine and PARKIN. Afterwards, PARKIN mediates the ubiquitination of the OMM, tagging it for p62 binding, which is linked to the autophagosomal LC3 protein, leading eventually to the targeting of the mitochondrion for mitophagy. DRP-1, dynamin-related protein-1; FIS1, fission 1 protein 1; PINK1, (PTEN)-induced putative kinase 1; LC3, microtubule-associated protein 1 A/1B-light chain 3; p62, ubiquitin-binding protein 62.