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

authored by
Marta Luna-Sánchez, Agustín Hidalgo-Gutiérrez, Tatjana M. Hildebrandt, Julio Chaves-Serrano, Eliana Barriocanal-Casado, Ángela Santos-Fandila, Miguel Romero, Ramy K.A. Sayed, Juan Duarte, Holger Prokisch, Markus Schuelke, Felix Distelmaier, Germaine Escames, Darío Acuña-Castroviejo, Luis C. López
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 Coq9R239X 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.

Organisation(s)
Institute of Plant Genetics
External Organisation(s)
University of Granada
Abbott Laboratories (Granada)
Sohag University
Technical University of Munich (TUM)
Charité - Universitätsmedizin Berlin
University Hospital Düsseldorf
Type
Article
Journal
EMBO molecular medicine
Volume
9
Pages
78-95
No. of pages
18
ISSN
1757-4676
Publication date
01.01.2017
Publication status
Published
Peer reviewed
Yes
ASJC Scopus subject areas
Molecular Medicine
Electronic version(s)
https://doi.org/10.15252/emmm.201606345 (Access: Open)