Mitophagy mediated by PINK1 and Parkin. Fusion/fission is required for the maintenance of a healthy mitochondrial population. Mitochondrial fusion is thought to require the exchange of a set of internal components, including copies of the mitochondrial genome, respiratory proteins, and metabolic products. Mitochondrial fission may play a role in the removal of damaged mitochondria (1, 2) with a reduced Δψm through an autophagy-lysosomal pathway, that is, “mitophagy.” PINK1 is constitutively degraded in healthy mitochondria (see also Figure 3). Upon a decrease in Δψm, PINK1 is stabilized in the mitochondrial outer membrane (OM) (3). The accumulation of PINK1 induces the translocation of Parkin from the cytosol to the mitochondria (3), which leads to Parkin-dependent mitochondrial protein degradation, through which Mfn is degraded to prevent healthy mitochondria from refusing with damaged mitochondria (4). Parkin subsequently activates the autophagy machinery, which includes induction of the isolation membrane for autophagy (5).