{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ETHE1 is a mitochondrial enzyme that functions as a sulfur dioxygenase, catalyzing the oxidation of reactive sulfur species (such as glutathione persulfide) derived from hydrogen sulfide. This reaction is essential for detoxifying hydrogen sulfide within the mitochondrial matrix, thereby protecting cytochrome c oxidase and other iron‐dependent enzymes from sulfide‐mediated inhibition. Loss‐of‐function mutations in the ETHE1 gene lead to an accumulation of hydrogen sulfide and thiosulfate, which in turn disrupts mitochondrial energy metabolism and redox homeostasis, ultimately producing the severe clinical syndrome known as ethylmalonic encephalopathy. In affected patients and corresponding animal models, ETHE1 deficiency is associated with multi‐system pathology—including early-onset encephalopathy, microangiopathy and chronic diarrhea—attributable to both direct inhibition of mitochondrial respiration and secondary oxidative stress. Moreover, increased ETHE1 activity (or its overexpression) has been shown to augment sulfur dioxygenase activity, reinforcing its central role in maintaining mitochondrial homeostasis and influencing cellular bioenergetics. Recent studies also suggest that ETHE1 might have broader metabolic significance, as its expression is altered in certain cancers (for example, colon adenocarcinoma) where changes in sulfide and polysulfide metabolism could modulate tumor cell bioenergetics. Overall, these findings underscore that ETHE1 is a critical component of the mitochondrial sulfide oxidation pathway, whose proper function is indispensable for preserving not only energy production and redox balance, but also overall cellular and tissue integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Valeria Tiranti, Carlo Viscomi, Tatjana Hildebrandt, et al. 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