Figure 10.

Schematic diagram shows that CS induces mitochondrial dysfunction and mitophagy impairment leading to cellular senescence via suborganellar signaling in COPD. CS stress causes mitochondrial elongation and dysfunction (i.e., ATP reduction and increased ROS release), leading to perinuclear accumulation of damaged mitochondria and DNA damage-initiated cellular senescence via suborganellar signaling during the development of COPD. CS exposure also increases the interaction of p53 with Parkin, which impairs Parkin-dependent mitophagy and further augments perinuclear mitochondrial clustering. Parkin overexpression along with MitoT treatment reduces mitophagy impairment and cellular senescence. Red dots indicate ROS.