Oxidative Stress-Derived Mitochondrial Dysfunction in Chronic Obstructive Pulmonary Disease: A Concise Review

Figure 2

Mitophagy regulation. In healthy mitochondria, the kinase PINK1 is constitutively repressed by import into the inner mitochondrial membrane (IMM) and degradation by the rhomboid protease PARL. In uncoupled mitochondria, import of PINK1 into the IMM is avoided, so PINK1 is bypassed from PARL and accumulates in the outer mitochondrial membrane (OMM), acting as a signal to mark dysfunctional mitochondria for Parkin, which then conjugates ubiquitin (Ub) to several proteins on the OMM and mediates proteasomal degradation of mitofusins 1 and 2. Finally, Parkin induces engulfment of the damaged mitochondria by autophagy compartments. Several proteins, including autophagy-related genes (ATGs), beclin-1, microtubule-associated protein 1 light-chain 3 (LC3), and p62, facilitate the formation of autophagosomes.