Sqor, or sulfide:quinone oxidoreductase, is a mitochondrial inner membrane protein. It plays a crucial role in the metabolism of hydrogen sulfide (H₂S), catalyzing the oxidation of H₂S to sulfane sulfur using coenzyme Q as an electron acceptor. This is part of the mitochondrial sulfide oxidation pathway, which is important for preventing H₂S-induced respiratory poisoning. SQOR is also involved in multiple biological processes and disease-related pathways, such as ferroptosis, hypoxia-related injury, and angiogenesis [1,2,3,4]. Genetic models, especially KO/CKO mouse models, are valuable for studying its function.

In Sqor-deletion mice, cisplatin-induced kidney impairment and ferroptosis in renal tubular epithelial cells were exacerbated, suggesting SQOR alleviates ferroptosis in acute kidney injury by ameliorating mitochondrial dysfunction [2]. Silencing SQOR in mice increased the brain's sensitivity to hypoxia, while neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury, indicating its role in protecting against hypoxic brain injury [3]. Tumor xenografts in Sqor-knockout mice had lower mass and angiogenesis, showing SQOR promotes hypoxic angiogenesis and neovascularization [4]. Mice with a mutation preventing SQOR from entering mitochondria had clinical and pathological manifestations of Leigh-like disease, and treatment with metronidazole or a sulfur-restricted diet could rescue them, suggesting SQOR deficiency is a cause of Leigh-like disease and these could be therapeutic approaches [5].

In conclusion, SQOR is essential for maintaining normal physiological functions through its role in H₂S metabolism. Model-based research, especially KO/CKO mouse models, has revealed its significance in various disease conditions such as acute kidney injury, hypoxic brain injury, angiogenesis-related diseases, and Leigh-like disease. Understanding SQOR function provides potential therapeutic targets for these diseases.