{"doi":"10.1101/2021.09.08.459449","title":"A redox cycle with complex II promotes sulfide quinone oxidoreductase dependent H <sub>2</sub> S oxidation","abstract":"The dueling roles of H 2 S as an endogenously synthesized respiratory substrate and as a toxin, raise questions as to how it is cleared when the electron transport chain is inhibited. Sulfide quinone oxidoreductase (SQOR) is a mitochondrial inner membrane flavoprotein that catalyzes the first step in the H 2 S oxidation pathway and uses coenzyme Q (CoQ) as an electron acceptor. However, complex IV poisoning by H 2 S inhibits complex III-dependent recycling of CoQH 2 , which is needed to sustain H 2 S oxidation. We have discovered that under these conditions, reversal of complex II activity using fumarate as an electron acceptor, establishes a new redox cycle with SQOR. The purine nucleotide cycle and the malate aspartate shuttle are sources of fumarate in H 2 S treated cells, which accumulate succinate. Complex II knockdown decreases the efficiency of H 2 S clearance and increases recovery time to the basal respiration rate in H 2 S treated cells. In contrast, attenuation of complex I, which is a major competitor for the mitochondrial CoQ pool, has the opposite effects. Targeted knockout of complex II in murine intestinal epithelial cells that are routinely exposed to microbiota derived H 2 S, decreases serum, urine, and fecal thiosulfate, a product of H 2 S oxidation. Our study identifies a metabolic reprogramming response to H 2 S that furnishes fumarate as an alternate electron acceptor and supports H 2 S oxidation independent of complex IV activity. Complex II-linked redox cycling of SQOR has important implications for gut H 2 S metabolism as colonocytes are routinely exposed to high concentrations of this gas derived from the microbiota. One Sentence Summary Reversal of complex II sustains and prioritizes H 2 S oxidation when respiration is poisoned.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221589,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":265992,"name":"Aaron P. Landry","orcid":"0000-0003-1161-7092","position":1,"is_corresponding":false},{"id":647270,"name":"Arkajit Guha","orcid":null,"position":2,"is_corresponding":false},{"id":350208,"name":"Victor Vitvitsky","orcid":"0000-0001-6251-6115","position":3,"is_corresponding":false},{"id":106330,"name":"Ho‐Joon Lee","orcid":"0000-0003-3616-5387","position":4,"is_corresponding":false},{"id":646484,"name":"Keisuke Seike","orcid":"0000-0002-3484-0265","position":5,"is_corresponding":false},{"id":385969,"name":"Pavan Reddy","orcid":"0000-0001-7264-8429","position":6,"is_corresponding":false},{"id":106351,"name":"Costas A. Lyssiotis","orcid":"0000-0001-9309-6141","position":7,"is_corresponding":false},{"id":265994,"name":"Ruma Banerjee","orcid":"0000-0001-8332-3275","position":8,"is_corresponding":false},{"id":31917,"name":"Roshan Kumar","orcid":"0000-0002-5372-8682","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:53:55.215284Z","pmid":null,"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":[]}