Reactive oxygen species–mitochondrial dysfunction–autophagy axis (ROS–mitochondrial dysfunction–autophagy axis)

The Reactive oxygen species (ROS)–mitochondrial dysfunction–autophagy axis is a complex biological signaling network that integrates cellular stress sensing with organelle quality control. In this axis, excessive ROS—primarily generated as byproducts of the mitochondrial electron transport chain—induce oxidative damage to mitochondrial proteins, lipids, and DNA, leading to a loss of mitochondrial membrane potential and further ROS leakage (Murphy, 2009, Biochem J, PMID: 19128243). To prevent the accumulation of these dysfunctional organelles and subsequent apoptosis, the cell activates autophagy, specifically a selective form called mitophagy, which is often mediated by the PINK1/Parkin pathway or BNIP3/NIX receptors (Youle & Narendra, 2011, Nat Rev Mol Cell Biol, PMID: 21179060). This axis plays a dual role in human pathology: while its impairment contributes to the accumulation of damaged mitochondria in neurodegenerative diseases like Parkinson's, its overactivation can promote the survival of cancer cells under nutrient-deprived or hypoxic conditions (Scherz-Shouval & Elazar, 2011, Trends Biochem Sci, PMID: 21145745). Therapeutic strategies targeting this axis include the use of mitochondria-targeted antioxidants like MitoQ to quench ROS, or autophagy modulators like Rapamycin and Metformin to restore homeostatic clearance of damaged mitochondria (Li et al., 2015, Autophagy, PMID: 25906140).

Other names

ROS-mitophagy axisOxidative stress-mitochondrial damage-autophagy pathwayROS-mitochondrial-autophagy signalingMitochondrial ROS-autophagy crosstalk

Modulation of oxidative stress levels, stabilization of mitochondrial membrane potential, and regulation of autophagic flux via mTOR or AMPK pathways to maintain cellular proteostasis.