{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSulfide:quinone oxidoreductase (SQOR) is a mitochondrial, membrane‐bound flavoprotein that initiates the detoxification of hydrogen sulfide (H₂S) by catalyzing its two‐electron oxidation. In this reaction, H₂S is converted into a sulfane sulfur species (a persulfide form) while electrons are transferred via the bound FAD cofactor to coenzyme Q in the electron transport chain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic investigations have revealed that SQOR can utilize different small-molecule sulfur acceptors. While earlier studies highlighted sulfite as an efficient acceptor at near-physiological pH, subsequent kinetic analyses have demonstrated that glutathione also functions as a physiological persulfide acceptor. These observations indicate that during normal H₂S oxidation the enzyme channels sulfur via glutathione persulfide formation, which can then be partitioned into downstream metabolites such as thiosulfate and sulfite; furthermore, alternate routes involving sulfite addition may occur under conditions of elevated sulfite concentrations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSQOR activity is tightly coupled to mitochondrial bioenergetics, given its role in transferring electrons to coenzyme Q. Perturbations in this enzyme’s function—whether due to a primary deficiency or as a consequence of coenzyme Q shortage—lead to H₂S accumulation and subsequent inhibition of complex IV of the electron transport chain. This impaired electron flow has been associated with metabolic crises and neurodegenerative presentations, as exemplified by patient cases where SQOR mutations resulted in lactic acidosis and Leigh-like syndromes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent structural studies, including those using nanodisc-embedded preparations and high-resolution crystallography, have unveiled unique features of SQOR. An electropositive surface depression appears to guide negatively charged sulfur acceptors toward a hydrophilic active site that links to a hydrophobic tunnel—ideal for coenzyme Q binding—thus defining a molecular framework for sulfane sulfur transfer reactions and offering new opportunities for structure-based drug design."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, genetic studies of the closely related SQRDL gene have implicated SQOR-like variants in modulating osteoblast differentiation and susceptibility to osteoporosis, emphasizing the enzyme’s diverse biological significance beyond H₂S detoxification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael R Jackson, Scott L Melideo, Marilyn Schuman Jorns "}, {"type": "b", "children": [{"type": "t", "text": "Human sulfide:quinone oxidoreductase catalyzes the first step in hydrogen sulfide metabolism and produces a sulfane sulfur metabolite."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi300778t"}], "href": "https://doi.org/10.1021/bi300778t"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22852582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22852582"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marouane Libiad, Pramod Kumar Yadav, Victor Vitvitsky, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Mol Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/emmm.201606345"}], "href": "https://doi.org/10.15252/emmm.201606345"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27856619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27856619"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marisa W Friederich, Abdallah F Elias, Alice Kuster, et al. 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