Hydrogen Sulfide Oxidation by Sulfide Quinone Oxidoreductase

Abstract

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.

The mitochondrial NADH pool is involved in hydrogen sulfide signaling and stimulation of aerobic glycolysis

“…5B,C). Approximately 3.5-fold higher 14 CO 2 was released from C1 versus C6 glucose in HCEC cells and ~9fold more in HT29 cells, indicating that the oxidative pentose phosphate pathway rather than the TCA cycle is the major source of CO 2 in both these cell lines.…”

“…Author contributions-VV-kinetics of H 2 S induced metabolite changes and Western blot analysis of PDH phosphorylation; RK-generation of cells expressing LbNOX, GOT1 KD, GOT2 KD and kinetics of sulfide consumption and thiosulfate accumulation; ML-analysis of sulfide effect on CO 2 production from [1- 14 C] and [6-14 C] glucose; AM-measurements of glucose consumption and lactate production rates; ALgeneration of ETHE1 KD cells; RB-experimental conception, data analysis, manuscript writing. VV and RB drafted the manuscript and all authors edited and approved the final version of the manuscript.…”

“…The oxidation pathway begins with the conversion of H 2 S to a persulfide in a reaction catalyzed by the inner mitochondrial membrane protein, sulfide quinone oxidoreductase (SQOR) (12,13). The electrons from this reaction are transferred via coenzyme Q to the ETC, and enter at the level of complex III (14). The glutathione persulfide product of the SQOR reaction (13,15,16), is oxidized by ETHE1 (17) to sulfite, which is either oxidized to sulfate by sulfite oxidase or converted to thiosulfate by thiosulfate sulfurtransferase (or rhodanese) (18).…”

Luteorhabdos pelagi gen. nov., sp. nov., a novel member of the family Flavobacteriaceae, isolated from the West Pacific Ocean

“…Coding genes related to sulfate reduction and hydrogen sul de oxidation were found in the draft genome of strain A3-108 T , including sulfate adenylyltransferase (cysND), adenylylsulfate kinase (cysC), and phosphoadenosine phosphosulfate reductase (cysH), indicating that strain A3-108 T could reduce sulfate to sul te. The sul de: quinone oxidoreductase (sqr) was also present, which could oxidize hydrogen sul de to sulfur (Landry et al, 2021). Additionally, relevant genes about sulfur metabolism thiosulfate dehydrogenase (quinone) large subunit (doxD) and heterodisul de reductase (hdrD) were detected.…”

Pathogenic variants in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease

“…16 The sulfane sulfur from this persulfide intermediate is then transferred to the physiological acceptor glutathione forming glutathione persulfide (GSSH). 17,18 In vitro, sulfite, cyanide, and other acceptors can substitute for glutathione forming thiosulfate, thiocyanate, and other products. 17 Glutathione persulfide is oxidized by persulfide dioxygenase (encoded by the gene ETHE1, pathogenic variants in this gene are implicated in ethylmalonic encephalopathy) to sulfite, which can be further oxidized to sulfate by sulfite oxidase or metabolized by thiosulfate sulfurtransferase to thiosulfate.…”