Hydrogen sulfide perturbs mitochondrial bioenergetics and triggers metabolic reprogramming in colon cells
Hydrogen sulfide perturbs mitochondrial bioenergetics and triggers metabolic reprogramming in colon cells
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DOI：
10.1074/jbc.ra119.009442
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发表时间：
2019-08-09
影响因子：
4.8
通讯作者：
Banerjee, Ruma
中科院分区：
文献类型：
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作者：
Libiad, Marouane;Vitvitsky, Victor;Banerjee, Ruma
与大多数其他组织不同，结肠上皮暴露在肠道微生物代谢产生的高水平硫化氢中。硫化氢是一种调节多种生理效应的信号分子。它也是一种呼吸道毒素，能抑制电子转移链(ETC)中的复合体IV。结肠上皮细胞适应高环境的H_2S暴露，因为它们拥有一个有效的线粒体H_2S氧化途径，这是专门用于处理它的。在这里，我们报告硫化物氧化途径酶位于宿主-微生物组界面的人结肠隐窝的顶端，但在结直肠癌上皮中丢失了正常的顶端到隐窝的梯度。我们发现，硫代苯醌氧化还原酶(SQR)催化线粒体硫化物氧化途径中的提交步骤，并偶联到复合体III，是抵御H_2S中毒的关键呼吸屏障。浓度下的硫化氢
Unlike most other tissues, the colon epithelium is exposed to high levels of H2S derived from gut microbial metabolism. H2S is a signaling molecule that modulates various physiological effects. It is also a respiratory toxin that inhibits complex IV in the electron transfer chain (ETC). Colon epithelial cells are adapted to high environmental H2S exposure as they harbor an efficient mitochondrial H2S oxidation pathway, which is dedicated to its disposal. Herein, we report that the sulfide oxidation pathway enzymes are apically localized in human colonic crypts at the host-microbiome interface, but that the normal apical-to-crypt gradient is lost in colorectal cancer epithelium. We found that sulfide quinone oxidoreductase (SQR), which catalyzes the committing step in the mitochondrial sulfide oxidation pathway and couples to complex III, is a critical respiratory shield against H2S poisoning. H2S at concentrations