The dueling roles of H₂S as an endogenously synthesized respiratory substrate and as a toxin, raise questions as to how it is cleared when the electron transport chain is inhibited. Sulfide quinone oxidoreductase (SQOR) is a mitochondrial inner membrane flavoprotein that catalyzes the first step in the H₂S oxidation pathway and uses coenzyme Q (CoQ) as an electron acceptor. However, complex IV poisoning by H₂S inhibits complex III-dependent recycling of CoQH₂, which is needed to sustain H₂S oxidation. We have discovered that under these conditions, reversal of complex II activity using fumarate as an electron acceptor, establishes a new redox cycle with SQOR. The purine nucleotide cycle and the malate aspartate shuttle are sources of fumarate in H₂S treated cells, which accumulate succinate. Complex II knockdown decreases the efficiency of H₂S clearance and increases recovery time to the basal respiration rate in H₂S treated cells. In contrast, attenuation of complex I, which is a major competitor for the mitochondrial CoQ pool, has the opposite effects. Targeted knockout of complex II in murine intestinal epithelial cells that are routinely exposed to microbiota derived H₂S, decreases serum, urine, and fecal thiosulfate, a product of H₂S oxidation. Our study identifies a metabolic reprogramming response to H₂S that furnishes fumarate as an alternate electron acceptor and supports H₂S oxidation independent of complex IV activity. Complex II-linked redox cycling of SQOR has important implications for gut H₂S metabolism as colonocytes are routinely exposed to high concentrations of this gas derived from the microbiota.

中文翻译：

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复合物 II 的氧化还原循环促进硫化醌氧化还原酶依赖的 H2S 氧化

H ₂ S 作为内源性合成呼吸底物和毒素的双重作用引发了关于当电子传递链受到抑制时如何清除H ₂ S 的问题。硫化醌氧化还原酶 (SQOR) 是一种线粒体内膜黄素蛋白，可催化 H ₂ S 氧化途径的第一步，并使用辅酶 Q (CoQ) 作为电子受体。然而，H ₂ S 对复合物 IV 的中毒抑制了 CoQH ₂依赖复合物 III 的循环，而 CoQH ₂是维持 H ₂所必需的S氧化。我们发现，在这些条件下，使用富马酸盐作为电子受体来逆转复合物 II 的活性，建立了一个新的 SQOR 氧化还原循环。嘌呤核苷酸循环和苹果酸天冬氨酸穿梭是 H ₂ S 处理的细胞中富马酸的来源，其积累琥珀酸。在 H ₂ S 处理的细胞中，复合物 II 敲低降低了 H ₂ S 清除效率并增加了恢复到基础呼吸率的时间。相比之下，作为线粒体 CoQ 池的主要竞争对手的复合物 I 的衰减具有相反的效果。在常规暴露于微生物群衍生的 H _{2 的}鼠肠上皮细胞中靶向敲除复合物 IIS，减少血清、尿液和粪便硫代硫酸盐（H ₂ S 氧化的产物）。我们的研究确定了对 H ₂ S的代谢重编程反应，该反应提供富马酸盐作为替代电子受体并支持 H ₂ S 氧化，而与复合物 IV 活性无关。SQOR 的复杂 II 相关氧化还原循环对肠道 H ₂ S 代谢具有重要意义，因为结肠细胞经常暴露于来自微生物群的高浓度这种气体。