FIGURE 4: Dysfunctional mitochondria are targeted to mitophagy. (A) Healthy mitochondria have a polarized outer mitochondrial membrane (OMM), which allows PTEN-induced kinase 1 (PINK1) to cross the membrane and be degraded by presenilin-associated rhomboid-like protein (PARL) at the inner mitochondrial membrane (IMM). (B) Impaired mitochondria, instead, have a depolarized OMM, which hinders the entry of PINK1 and, therefore, its degradation. PINK1 can thus bind to parkin to initiate mitophagy. MPP- matrix-processing peptidase; TIM – translocase of inner mitochondrial membrane; TOM – translocase of outer mitochondrial membrane.