Mitochondrial reactive oxygen species pathway (mtROS pathway)

The mitochondrial reactive oxygen species (ROS) pathway refers to the biochemical processes involved in the generation, signaling, and detoxification of oxygen-derived free radicals within the mitochondria [17, 18]. Primarily produced as by-products of the electron transport chain (ETC) during oxidative phosphorylation, mitochondrial ROS (mtROS) like superoxide and hydrogen peroxide act as critical signaling molecules at low concentrations, regulating cellular adaptation to stress and metabolic needs [17, 18]. However, excessive mtROS production or impaired antioxidant defense leads to oxidative stress, causing damage to mitochondrial DNA, proteins, and lipids, which is a hallmark of various pathologies including neurodegenerative diseases, cancer, and cardiovascular disorders [1, 8, 10]. Therapeutic strategies targeting this pathway often involve mitochondria-targeted antioxidants (e.g., MitoQ, SS-31) that scavenge ROS or agents that modulate ETC activity to prevent electron leakage [2, 4, 6]. While promising, targeting these pathways presents challenges, as complete suppression of ROS can interfere with essential physiological signaling and cellular homeostasis [9, 16]. Additionally, the narrow therapeutic window of many mitochondrial agents necessitates careful dosing to avoid disrupting ATP production or inducing mitochondrial depolarization [10].

Other names

mROS pathwayMitochondrial oxidative stress pathwayMitochondrial redox signaling pathway

Scavenging of mitochondrial superoxide and hydrogen peroxide, inhibition of electron transport chain complexes (e.g., Complex I or III), stabilization of mitochondrial membranes, and modulation of the mitochondrial permeability transition pore (mPTP).