RT Journal Article
T1 CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome.
A1 Luna-Sanchez, Marta
A1 Hidalgo-Gutierrez, Agustín
A1 Hildebrandt, Tatjana M
A1 Chaves-Serrano, Julio
A1 Barriocanal-Casado, Eliana
A1 Santos-Fandila, Angela
A1 Romero, Miguel
A1 Sayed, Ramy Ka
A1 Duarte, Juan
A1 Prokisch, Holger
A1 Schuelke, Markus
A1 Distelmaier, Felix
A1 Escames, Germaine
A1 Acuña-Castroviejo, Dario
A1 Lopez, Luis C
K1 COX
K1 SQR
K1 blood pressure
K1 glutathione
K1 mitochondrial disease
AB 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.
PB EMBO Press
YR 201-
FD 201-10-19
LK http://hdl.handle.net/10668/10613
UL http://hdl.handle.net/10668/10613
LA en
NO Luna-Sánchez M, Hidalgo-Gutiérrez A, Hildebrandt TM, Chaves-Serrano J, Barriocanal-Casado E, Santos-Fandila Á, et al. CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome. EMBO Mol Med. 2017 Jan;9(1):78-95.
NO We are grateful to Dr. Iryna Rusanova (Universidad de Granada) for her technical support. We thank to Pol Herrero (Metabolomics Facility at the Center for Omic Sciences (COS) of the University Rovira i Virgili, recognized as a Singular Research and Technology Infrastructure by the Spanish Ministry of Economy and Competitiveness) for his contributions to mass spectrometry analysis. This work was supported by grants from Ministerio de Economía y Competitividad, Spain, and the ERDF (SAF2013‐47761‐R, SAF2014‐55523‐R, RD12/0042/0011 and SAF2015‐65786‐R), from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (P10‐CTS‐6133), from the NIH (P01HD080642) and from the foundation “todos somos raros, todos somos únicos”. MLS is a predoctoral fellow from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía. LCL is supported by the “Ramón y Cajal” National Programme, Ministerio de Economía y Competitividad, Spain (RYC‐2011‐07643).
DS RISalud
RD Apr 19, 2025