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dc.contributor.authorGonzález-García, Pilar
dc.contributor.authorHidalgo-Gutiérrez, Agustín
dc.contributor.authorMascaraque Molina, Cristina 
dc.contributor.authorBarriocanal Casado, Eliana 
dc.contributor.authorBakkali, Mohammed 
dc.contributor.authorZiosi, Marcello
dc.contributor.authorAbdihankyzy, Ussipbek Botagoz
dc.contributor.authorSánchez Hernández, Sabina
dc.contributor.authorEscames Rosa, Germaine 
dc.contributor.authorProkisch, Holger
dc.contributor.authorMartín Molina, Francisco 
dc.contributor.authorQuinzii, Catarina M.
dc.contributor.authorLópez García, Luis Carlos
dc.identifier.citationPilar González-García, Agustín Hidalgo-Gutiérrez, Cristina Mascaraque, Eliana Barriocanal-Casado, Mohammed Bakkali, Marcello Ziosi, Ussipbek Botagoz Abdihankyzy, Sabina Sánchez-Hernández, Germaine Escames, Holger Prokisch, Francisco Martín, Catarina M Quinzii, Luis C López, Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolism, Human Molecular Genetics, Volume 29, Issue 19, 1 October 2020, Pages 3296–3311, []es_ES
dc.descriptionThis work was supported by grants from Ministerio de Ciencia e Innovacion, Spain, and the ERDF (RTI2018-093503-B-100); the Muscular Dystrophy Association (MDA-602322); the University of Granada (grant reference 'UNETE', UCE-PP2017-06) (L.C.L.) and the National Institute of Health (NIH, United States) P01 HD080642-01 (C.M.Q.). A.H.-G. and P.G.-G. are `FPU fellows' from the Ministerio de Universidades, Spain. E.B.-C. was supported by the Junta de Andalucia. U.B.A. was supported by the Erasmus+ Program.es_ES
dc.description.abstractAbnormalities 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.es_ES
dc.description.sponsorshipSpanish Governmentes_ES
dc.description.sponsorshipEuropean Union (EU) RTI2018-093503-B-100es_ES
dc.description.sponsorshipMuscular Dystrophy Association MDA-602322es_ES
dc.description.sponsorshipUniversity of Granada UCE-PP2017-06es_ES
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA P01 HD080642-01es_ES
dc.description.sponsorshipJunta de Andaluciaes_ES
dc.description.sponsorshipErasmus+ Programes_ES
dc.publisherOxford University Presses_ES
dc.rightsAtribución-NoComercial 3.0 España*
dc.titleCoenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolismes_ES

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