Mitochondrial oxidoreductase enzymes

Mitochondrial oxidoreductase enzymes encompass a class of proteins, primarily the transmembrane complexes I (NADH:ubiquinone oxidoreductase), II (succinate dehydrogenase), and III (ubiquinol-cytochrome c oxidoreductase) of the electron transport chain, that catalyze electron transfer from donors like NADH to acceptors such as ubiquinone or cytochrome c, using NAD+ or NADP+ cofactors. These enzymes drive proton translocation across the inner mitochondrial membrane, generating the proton motive force essential for ATP synthesis via oxidative phosphorylation and regulating cellular energy metabolism. They also contribute to reactive oxygen species (ROS) production and detoxification, influencing signaling pathways like apoptosis and oxidative stress responses. Dysfunctions in these enzymes are implicated in diseases including cancer (via altered ferroptosis or apoptosis), neurodegenerative disorders (e.g., Parkinson's via ROS), and ischemia-reperfusion injury. Pharmacological targeting focuses on mitochondrion-selective antioxidants like MitoQ or peptides like SS-31 to mitigate ROS, or inhibitors like brequinar for DHODH to induce cancer cell death, though challenges include precise delivery to avoid cytosolic interference. Overall, while not a single target, they represent a broad therapeutic avenue in mitochondrial medicine.

Other names

Respiratory chain complexes I-IIINADH:ubiquinone oxidoreductase (complex I)Succinate dehydrogenase (complex II)Ubiquinol-cytochrome c oxidoreductase (complex III)Electron transport chain enzymes

Mitochondrial-targeted antioxidant activity, ROS scavenging, Ferroptosis induction (via DHODH inhibition), MPT inhibition, Proapoptotic effects, Membrane potential disruption