Sqor, short for sulfide:quinone oxidoreductase, is a mitochondrial inner membrane protein. It plays a crucial role in sulfide catabolism, catalyzing the oxidation of hydrogen sulfide (H₂S) using coenzyme Q as an electron acceptor in the mitochondrial sulfide oxidation pathway [6,7]. This function is vital for preventing H₂S-induced inhibition of complex IV in the electron transport chain, thus maintaining normal mitochondrial function and energy metabolism. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In Sqor-deletion mice, cisplatin-induced kidney impairment and ferroptosis in renal tubular epithelial cells were exacerbated, indicating that Sqor alleviates ferroptosis in acute kidney injury by ameliorating mitochondrial dysfunction [1]. Mice with a mutation preventing SQOR from entering mitochondria showed clinical and pathological manifestations of Leigh-like disease, with increased blood lactate and H₂S levels, and decreased complex IV activity [4]. Silencing SQOR in mice increased the sensitivity of the brain to hypoxia, while neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury [2,5]. Tumor xenografts in Sqor-knockout mice had lower mass and angiogenesis, suggesting SQOR promotes hypoxic angiogenesis and neovascularization [3].

In conclusion, Sqor is essential for maintaining mitochondrial function and energy homeostasis through sulfide catabolism. Studies using Sqor KO/CKO mouse models have revealed its significance in diseases like acute kidney injury, Leigh syndrome, hypoxic brain injury, and angiogenesis-related disorders, providing potential therapeutic targets for these conditions.