CoQ Deficiency Causes Disruption of Mitochondrial Sulfide Oxidation, a New Pathomechanism Associated with This Syndrome

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2016 Nov 19

PMID 27856619

Citations 38

Authors

Marta Luna-Sanchez

Agustin Hidalgo-Gutierrez

Tatjana M Hildebrandt

Julio Chaves-Serrano

Eliana Barriocanal-Casado

Angela Santos-Fandila

Miguel Romero

Ramy Ka Sayed

Juan Duarte

Holger Prokisch

Markus Schuelke

Felix Distelmaier

Germaine Escames

Dario Acuna-Castroviejo

Luis C Lopez

Affiliations

Soon will be listed here.

Abstract

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 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.

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