Longevity & AgingMitochondrial ROS Activates DNA Damage Pathway to Drive Protective Mitophagy
Researchers at China Medical University and University of Pittsburgh discovered that mitochondrial reactive oxygen species (mtROS) act as signaling molecules that activate the ATM-CHK2 DNA damage response (DDR) pathway to drive PINK1/Parkin-dependent mitophagy. CHK2, once activated, phosphorylates three distinct targets: ATAD3A (blocking PINK1 import to initiate mitophagy), OPTN (enhancing recognition of ubiquitinated mitochondria by autophagosomes), and Beclin 1 (promoting autophagosome membrane formation). In CHK2-knockout mice, mitophagy induction was impaired and recovery from renal ischemia-reperfusion injury — a ROS-dependent model — was significantly diminished, demonstrating in vivo relevance.
