CoQ10 oxidoreductases in ferroptosis and cancer: redox regulation and therapeutic opportunities

Abstract

Coenzyme Q10 (CoQ10) is a highly conserved lipophilic redox cofactor that mediates electron transport in mitochondria and protects cells against oxidative stress. Increasing evidence has revealed that CoQ10 and its associated oxidoreductases serve as critical regulators of ferroptosis—an iron-dependent, lipid peroxidation-driven form of cell death. Here we provide an updated overview of the canonical CoQ10 biosynthetic pathway and the established functions of key CoQ10 oxidoreductases. We highlight emerging insights into ferroptosis-suppressive roles of enzymes such as FSP1, DHODH and SQOR, which act by regenerating ubiquinol (CoQ10H2, reduced). In addition, we discuss newly identified CoQ10-related enzymes and their mechanistic contributions to ferroptosis regulation. By integrating perspectives from biochemistry, metabolism and cancer biology, this review positions CoQ10 oxidoreductases as promising targets for ferroptosis-based cancer therapies.