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In 2020, mutations in the gene encoding sulfide:quinone oxidoreductase (SQOR), a mitochondrial protein, were identified as a cause of Leigh syndrome. Here, we report that mice with a mutation in the gene encoding SQOR (Sqor\n                    <jats:sup>\u0394N\/\u0394N<\/jats:sup>\n                    mice), which prevented SQOR from entering mitochondria, had clinical and pathological manifestations of Leigh syndrome. Sqor\n                    <jats:sup>\u0394N\/\u0394N<\/jats:sup>\n                    mice had increased blood lactate levels that were associated with markedly decreased complex IV activity and increased hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) levels. Because H\n                    <jats:sub>2<\/jats:sub>\n                    S is produced by both gut microbiota and host tissue, we tested whether metronidazole (a broad-spectrum antibiotic) or a sulfur-restricted diet rescues Sqor\n                    <jats:sup>\u0394N\/\u0394N<\/jats:sup>\n                    mice from developing Leigh syndrome. Daily treatment with metronidazole alleviated increased H\n                    <jats:sub>2<\/jats:sub>\n                    S levels, normalized complex IV activity and blood lactate levels, and prolonged the survival of Sqor\n                    <jats:sup>\u0394N\/\u0394N<\/jats:sup>\n                    mice. Similarly, a sulfur-restricted diet normalized blood lactate levels and inhibited the development of Leigh syndrome. Taken together, these observations suggest that mitochondrial SQOR is essential to prevent systemic accumulation of H\n                    <jats:sub>2<\/jats:sub>\n                    S. Metronidazole administration and a sulfur-restricted diet may be therapeutic approaches to treatment of patients with Leigh syndrome caused by mutations in\n                    <jats:italic>SQOR<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1172\/jci170994","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T12:39:39Z","timestamp":1718282379000},"source":"Crossref","is-referenced-by-count":15,"title":["Exclusion of sulfide:quinone oxidoreductase from mitochondria causes Leigh-like disease in mice by impairing sulfide metabolism"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-723X","authenticated-orcid":true,"given":"Eiki","family":"Kanemaru","sequence":"first","affiliation":[{"name":"Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 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