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线粒体与硫化物:一个关于中毒、营养和信号转导的古老故事?

Mitochondria and sulfide: a very old story of poisoning, feeding, and signaling?

机构信息

Institut Cochin, Université Paris Descartes, INSERM-U1016, CNRS-UMR8104, Paris, France.

出版信息

Antioxid Redox Signal. 2011 Jul 15;15(2):379-91. doi: 10.1089/ars.2010.3678. Epub 2011 Apr 20.

DOI:10.1089/ars.2010.3678
PMID:21028947
Abstract

Sulfide is a molecule with toxicity comparable to that of cyanide. It inhibits mitochondrial cytochrome oxidase at submicromolar concentrations. However, at even lower concentrations, sulfide is a substrate for the mitochondrial electron transport chain in mammals, and is comparable to succinate. This oxidation involves a sulfide quinone reductase. Sulfide is thus oxidized before reaching a toxic concentration, which explains why free sulfide concentrations are very low in mammals, even though sulfide is constantly released as a result of cellular metabolism. It has been suggested that sulfide has signaling properties in mammals like two other gases, NO and CO, which are also cytochrome oxidase inhibitors. The oxidation of sulfide by mitochondria creates further complexity in the description/use of sulfide signaling in mammals. In fact, in the many studies reported in the literature, the sulfide concentrations that have been used were well within the range that affects mitochondrial activity. This review focuses on the relevance of sulfide bioenergetics to sulfide biology and discusses the case of colonocytes, which are routinely exposed to higher sulfide concentrations. Finally, we offer perspectives for future studies on the relationship between the two opposing aspects of this Janus-type molecule, sulfide.

摘要

硫化物是一种毒性与氰化物相当的分子。它在亚毫摩尔浓度下抑制线粒体细胞色素氧化酶。然而,在更低的浓度下,硫化物是哺乳动物线粒体电子传递链的底物,与琥珀酸盐相当。这种氧化涉及一种硫化物醌还原酶。因此,硫化物在达到毒性浓度之前就被氧化,这解释了为什么哺乳动物中自由硫化物的浓度非常低,尽管硫化物由于细胞代谢而不断释放。有人认为,硫化物像另外两种气体一氧化氮(NO)和一氧化碳(CO)一样,具有哺乳动物的信号传递特性,而这两种气体也是细胞色素氧化酶抑制剂。线粒体对硫化物的氧化,使哺乳动物中硫化物信号传递的描述/应用更加复杂。事实上,在文献中报道的许多研究中,所使用的硫化物浓度都在影响线粒体活性的范围内。本综述重点讨论了硫化物生物能量学与硫化物生物学的相关性,并讨论了结肠细胞的情况,结肠细胞通常会接触到更高浓度的硫化物。最后,我们为研究这种两面派分子(硫化物)的两个对立方面之间的关系提供了未来研究的视角。

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