Proposed models for CO action on mitochondria. (a) Under physiological conditions, 1–3% of the consumed oxygen is incompletely reduced to anion superoxide (), which is rapidly converted into hydrogen peroxide (H2O2) by the superoxide dismutase present in the mitochondrial matrix. (b) The most accepted hypothesis for CO to generate mitochondrial ROS is based on partially and/or reversely inhibition of cytochrome c oxidase (complex IV), leading to electron accumulation at complex III level, which facilitates anion superoxide generation. (c) Since low doses of CO also improve mitochondrial respiration, it can be speculated that CO induces mitochondrial ROS generation because oxidative phosphorylation is accelerated. The exact mitochondrial target is not fully understood, but complexes II and IV are strong candidates.
