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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolism
Human Molecular Genetics, Volume 29, No. 19, Year 2020
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Description
Abnormalities of one carbon, glutathione and sulfide metabolisms have recently emerged as novel pathomechanisms in diseases with mitochondrial dysfunction. However, the mechanisms underlying these abnormalities are not clear. Also, we recently showed that sulfide oxidation is impaired in Coenzyme Q10 (CoQ10) deficiency. This finding leads us to hypothesize that the therapeutic effects of CoQ10, frequently administered to patients with primary or secondary mitochondrial dysfunction, might be due to its function as cofactor for sulfide:quinone oxidoreductase (SQOR), the first enzyme in the sulfide oxidation pathway. Here, using biased and unbiased approaches, we show that supraphysiological levels of CoQ10 induces an increase in the expression of SQOR in skin fibroblasts from control subjects and patients with mutations in Complex I subunits genes or CoQ biosynthetic genes. This increase of SQOR induces the downregulation of the cystathionine β-synthase and cystathionine γ-lyase, two enzymes of the transsulfuration pathway, the subsequent downregulation of serine biosynthesis and the adaptation of other sulfide linked pathways, such as folate cycle, nucleotides metabolism and glutathione system. These metabolic changes are independent of the presence of sulfur aminoacids, are confirmed in mouse models, and are recapitulated by overexpression of SQOR, further proving that the metabolic effects of CoQ10 supplementation are mediated by the overexpression of SQOR. Our results contribute to a better understanding of how sulfide metabolism is integrated in one carbon metabolism and may explain some of the benefits of CoQ10 supplementation observed in mitochondrial diseases. © 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved.
Authors & Co-Authors
Hidalgo-Gutiérrez, Agustín
Spain, Granada
Universidad de Granada
Spain, Granada
Universidad de Granada, Facultad de Medicina
Barriocanal-Casado, Eliana
Spain, Granada
Universidad de Granada
Spain, Granada
Universidad de Granada, Facultad de Medicina
Bakkali, Mohammed
Spain, Granada
Universidad de Granada
Escames, Germaine
Spain, Granada
Universidad de Granada
Spain, Granada
Universidad de Granada, Facultad de Medicina
Prokisch, Holger
Germany, Munich
Technische Universität München
Martín, Francisco
Unknown Affiliation
Quinzii, Catarina Maria
United States, New York
Columbia University Irving Medical Center
López, Luís Carlos
Spain, Granada
Universidad de Granada
Spain, Granada
Universidad de Granada, Facultad de Medicina
Statistics
Citations: 15
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1093/hmg/ddaa214
ISSN:
09646906
Research Areas
Environmental
Noncommunicable Diseases