Reactive oxygen species (ROS)-mediated autophagy pathway (ROS-mediated autophagy)

The Reactive oxygen species (ROS)-mediated autophagy pathway is a complex cellular signaling network where ROS serve as essential messengers to initiate the autophagic process (Scherz-Shouval & Elazar, 2011, PubMed: 21390105). In response to oxidative stress, ROS can activate key regulators such as AMPK or inhibit the mTORC1 complex, which in turn triggers the assembly of the autophagy machinery to sequester and degrade damaged cellular components (Filomeni et al., 2015, PubMed: 25236395). This pathway primarily functions as a survival mechanism to maintain cellular integrity and homeostasis by clearing oxidatively damaged proteins and organelles like mitochondria (mitophagy) (Li et al., 2015, PubMed: 25601244). However, its role is context-dependent; while it prevents initial tumor formation, it can also be hijacked by established cancer cells to survive nutrient deprivation and chemotherapy (White, 2012, PubMed: 22447063). Consequently, therapeutic interventions targeting this pathway involve either the use of antioxidants to reduce ROS-driven autophagy or the application of autophagy inhibitors like chloroquine to sensitize diseased cells to treatment (Levy et al., 2017, PubMed: 28803353). Dysregulation of this pathway is also a hallmark of neurodegenerative diseases, where failure to clear ROS-damaged aggregates contributes to neuronal death (Nixon, 2013, PubMed: 23518310).

Other names

ROS-induced autophagyOxidative stress-induced autophagyROS-autophagy signaling axis

Modulation of the pathway occurs through the regulation of upstream signaling kinases (e.g., AMPK activation or mTOR inhibition), direct scavenging of reactive oxygen species, or pharmacological inhibition of autophagosome formation and lysosomal fusion (Galluzzi et al., 2017, PubMed: 28528230).