Sulfide:quinone oxidoreductase, mitochondrial (SQOR) (SQOR)

Sulfide:quinone oxidoreductase (SQOR) is a mitochondrial inner membrane flavoenzyme that catalyzes the first and rate-limiting step in the oxidation of hydrogen sulfide (H2S) (UniProt: Q9Y6N5; PubMed: 20303979). By transferring electrons from H2S to the ubiquinone pool, SQOR prevents the toxic accumulation of sulfide, which otherwise inhibits cytochrome c oxidase (Complex IV) and disrupts mitochondrial respiration (PubMed: 33203720). Beyond its role in detoxification, SQOR regulates the levels of H2S, a potent gasotransmitter that mediates various physiological processes, including cardioprotection and vasodilation, through the post-translational modification of proteins known as persulfidation (PubMed: 34132787). Recent research has identified SQOR as a promising therapeutic target for heart failure with reduced ejection fraction (HFrEF), where small-molecule inhibitors like STI1 are used to elevate H2S levels and activate protective pathways (PubMed: 34132787). Furthermore, SQOR contributes to ferroptosis resistance by functioning as a ubiquinone reductase, producing the antioxidant ubiquinol to quench lipid peroxides (PubMed: 38016644). Genetic mutations in the SQOR gene lead to SQOR deficiency, a severe metabolic disorder characterized by encephalopathy and Leigh-like syndrome due to systemic sulfide toxicity (OMIM: 619221).

Other names

Sulfide:quinone oxidoreductase (UniProt: Q9Y6N5)Sulfide quinone reductase-like (SQRDL)CGI-44SQRSulfide dehydrogenase-likePRO1975

Inhibition of SQOR increases endogenous hydrogen sulfide levels, which promotes cardioprotective signaling through protein persulfidation (PubMed: 34132787).