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

Figure 3

Impaired mitophagy in COPD. In regular conditions, cigarette smoke- (CS-) induced mitochondrial damage stabilizes PINK1 on the outer mitochondrial membrane (OMM), which signals for Parkin recruitment to the mitochondrion from an abundant cytosolic pool, leading to sufficient mitophagy, preventing the accumulation of dysfunctional mitochondria, and slowing cellular senescence. In COPD, decreased levels of cytosolic Parkin seem to be related to insufficient mitophagy, which increases the number of damaged mitochondria with stabilized PINK1, leading to further PRKN reduction by PINK1-mediated proteasomal degradation. In COPD, increased levels of p53, a cytosolic protein capable of inhibiting Parkin, may contribute to the reduced availability of Parkin molecules for proteasomal degradation of PINK1.