Hydrogen Sulfide Oxidation by Sulfide Quinone Oxidoreductase

• Published in: Chembiochem : a European journal of chemical biology 2021-03, Vol.22 (6), p.949-960
• Main Authors: Landry, Aaron P., Ballou, David P., Banerjee, Ruma
• Format: Article
• Language: English
• Subjects: Catalytic Domain; Coenzyme Q10; Electron transport; Electron transport chain; Electron Transport Complex IV - metabolism; flavins; Humans; Hydrogen sulfide; Hydrogen Sulfide - chemistry; Hydrogen Sulfide - metabolism; metabolism; Microorganisms; Mitochondria; Mitochondria - metabolism; Neuromodulation; Oxidation; Oxidation-Reduction; Oxidative Phosphorylation; Physiological responses; protein structure; Quinone oxidoreductase; Quinone Reductases - chemistry; Quinone Reductases - classification; Quinone Reductases - metabolism; Quinones; redox chemistry; Substrate Specificity; Substrates; sulfides; Toxins; Ubiquinone - analogs & derivatives; Ubiquinone - chemistry
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202000661

Hydrogen sulfide (H2S) is an environmental toxin and a heritage of ancient microbial metabolism that has stimulated new interest following its discovery as a neuromodulator. While many physiological responses have been attributed to low H2S levels, higher levels inhibit complex IV in the electron transport chain. To prevent respiratory poisoning, a dedicated set of enzymes that make up the mitochondrial sulfide oxidation pathway exists to clear H2S. The committed step in this pathway is catalyzed by sulfide quinone oxidoreductase (SQOR), which couples sulfide oxidation to coenzyme Q10 reduction in the electron transport chain. The SQOR reaction prevents H2S accumulation and generates highly reactive persulfide species as products; these can be further oxidized or can modify cysteine residues in proteins by persulfidation. Here, we review the kinetic and structural characteristics of human SQOR, and how its unconventional redox cofactor configuration and substrate promiscuity lead to sulfide clearance and potentially expand the signaling potential of H2S. This dual role of SQOR makes it a promising target for H2S‐based therapeutics. Regulating sulfide toxicity and signaling: Utilizing an active‐site cysteine trisulfide, human sulfide quinone oxidoreductase detoxifies hydrogen sulfide, a respiratory poison. Herein, we detail the remarkable enzymology of sulfide quinone oxidoreductase and its potential modulation of sulfide signaling.