CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome

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• 作者：Marta Luna-Sá ; nchez ; Agustí ; n Hidalgo-Guti&eacute ; rrez ; Tatjana M Hildebrandt ; Julio Chaves-Serrano ; Eliana Barriocanal-Casado ; Á ; ngela Santos-Fandila ; Miguel Romero ; Ramy KA Sayed ; Juan Duarte ; Holger Prokisch ; Markus Schuelke ; Felix Distelmaier ; Germaine Escames ; Darí ; o Acuñ ; a-Castroviejo and Luis C Ló ; pez
• 刊名：EMBO Molecular Medicine
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：9
• 期：1
• 页码：78-95
• 全文大小：3663K
• ISSN：1757-4684

文摘

Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain, but it also has several other functions in the cellular metabolism. One of them is to function as an electron carrier in the reaction catalyzed by sulfide:quinone oxidoreductase (SQR), which catalyzes the first reaction in the hydrogen sulfide oxidation pathway. Therefore, SQR may be affected by CoQ deficiency. Using human skin fibroblasts and two mouse models with primary CoQ deficiency, we demonstrate that severe CoQ deficiency causes a reduction in SQR levels and activity, which leads to an alteration of mitochondrial sulfide metabolism. In cerebrum of Coq9^R239X mice, the deficit in SQR induces an increase in thiosulfate sulfurtransferase and sulfite oxidase, as well as modifications in the levels of thiols. As a result, biosynthetic pathways of glutamate, serotonin, and catecholamines were altered in the cerebrum, and the blood pressure was reduced. Therefore, this study reveals the reduction in SQR activity as one of the pathomechanisms associated with CoQ deficiency syndrome.