{"doi":"10.1016/j.jbc.2022.101661","title":"Complexities of complex II: Sulfide metabolism in vivo","abstract":"High levels of H2S produced by gut microbiota can block oxygen utilization by inhibiting mitochondrial complex IV. Kumar et al. have shown how cells respond to this inhibition by using the mitochondrial sulfide oxidation pathway and reverse electron transport. The reverse activity of mitochondrial complex II (succinate-quinone oxidoreductase, i.e., fumarate reduction) generates oxidized coenzyme Q, which is then reduced by the mitochondrial sulfide quinone oxidoreductase to oxidize H2S. This newly identified redox circuitry points to the importance of complex II reversal in mitochondria during periods of hypoxia and cellular stress. High levels of H2S produced by gut microbiota can block oxygen utilization by inhibiting mitochondrial complex IV. Kumar et al. have shown how cells respond to this inhibition by using the mitochondrial sulfide oxidation pathway and reverse electron transport. The reverse activity of mitochondrial complex II (succinate-quinone oxidoreductase, i.e., fumarate reduction) generates oxidized coenzyme Q, which is then reduced by the mitochondrial sulfide quinone oxidoreductase to oxidize H2S. This newly identified redox circuitry points to the importance of complex II reversal in mitochondria during periods of hypoxia and cellular stress. It is generally accepted that mitochondria evolved from an endosymbiotic prokaryote (1Roger A.J. Munoz-Gomez S.A. Kamikawa R. The origin and diversification of mitochondria.Curr. Biol. 2017; 27: R1177-R1192Google Scholar). In eukaryotes, the chemical reactions of oxidative phosphorylation, the Krebs (tricarboxylic acid, TCA) cycle, and fatty acid oxidation are almost exclusively found within the mitochondrion. In mammals, the mitochondrion is considered to require oxygen as an electron acceptor to function for ATP production. In numerous lower eukaryotes, however, anaerobically functioning mitochondria are found which can use alternate electron acceptors (2Mentel M. Rottger M. Leys S. Tielens A.G. Martin W.F. Of early animals, anaerobic mitochondria, and a modern sponge.Bioessays. 2014; 36: 924-932Google Scholar). These lower eukaryotes and bacteria use specialized enzymes (e.g., quinone- or NADH-dependent fumarate reductase, nitrate reductase, etc.) and alternative electron carriers (e.g., rhodoquinone, menaquinone, etc.) to generate ATP and maintain metabolism. It could therefore be posited that mammalian mitochondria retain catalytic functions normally associated with lower eukaryotes that reside in anaerobic or microaerophilic environments. Kumar et al. (3Kumar R. Landry A.P. Guha A. Vitvitsky V. Lee H.J. Seike K. Reddy P. Lyssiotis C.A. Banerjee R. A redox cycle with complex II prioritizes sulfide quinone oxidoreductase dependent H2S oxidation.J. Biol. Chem. 2022; 298: 101435Google Scholar) have recently provided an interesting example of how mammalian intestinal epithelial cell mitochondria adapt to high levels of H2S produced environmentally by the microbiome by coupling sulfide quinone oxidoreductase (SQOR) and respiratory complex II (succinate dehydrogenase, SDH) activities. Sulfide quinone oxidoreductase and complex II are flavoproteins that are bound to the inner mitochondrial membrane, and both enzymes reduce coenzyme Q (CoQ) in their normal physiological activities. Complex II is unique in that it is the only membrane-bound component of the TCA cycle, but it is also a key component of the electron transport chain, providing reducing equivalents through ubiquinone reduction that are used by complex III (ubiquinol-cytochrome c reductase) and complex IV (cytochrome c oxidase) for oxidative phosphorylation. At high concentrations, H2S can act as electron transport chain toxin, inhibiting oxygen utilization by tightly binding to the heme of respiratory complex IV (cytochrome c oxidase) (4Landry A.P. Ballou D.P. Banerjee R. Hydrogen sulfide oxidation by sulfide quinone oxidoreductase.Chembiochem. 2021; 22: 949-960Google Scholar). Because H2S at lower concentratio","journal":"Journal of Biological Chemistry","year":2022,"id":283112,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":315279,"name":"Gary Cecchini","orcid":"0000-0002-0571-1747","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T00:29:23.777809Z","pmid":"35101450","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}