Details
| Original language | English |
|---|---|
| Pages (from-to) | 78-95 |
| Number of pages | 18 |
| Journal | EMBO molecular medicine |
| Volume | 9 |
| Issue number | 1 |
| Publication status | Published - 1 Jan 2017 |
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.
Keywords
- blood pressure, COX, glutathione, mitochondrial disease, SQR
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Medicine
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In: EMBO molecular medicine, Vol. 9, No. 1, 01.01.2017, p. 78-95.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome
AU - Luna-Sánchez, Marta
AU - Hidalgo-Gutiérrez, Agustín
AU - Hildebrandt, Tatjana M.
AU - Chaves-Serrano, Julio
AU - Barriocanal-Casado, Eliana
AU - Santos-Fandila, Ángela
AU - Romero, Miguel
AU - Sayed, Ramy K.A.
AU - Duarte, Juan
AU - Prokisch, Holger
AU - Schuelke, Markus
AU - Distelmaier, Felix
AU - Escames, Germaine
AU - Acuña-Castroviejo, Darío
AU - López, Luis C.
N1 - Funding information: 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).
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
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.
KW - blood pressure
KW - COX
KW - glutathione
KW - mitochondrial disease
KW - SQR
UR - http://www.scopus.com/inward/record.url?scp=85003702491&partnerID=8YFLogxK
U2 - 10.15252/emmm.201606345
DO - 10.15252/emmm.201606345
M3 - Article
C2 - 27856619
AN - SCOPUS:85003702491
VL - 9
SP - 78
EP - 95
JO - EMBO molecular medicine
JF - EMBO molecular medicine
SN - 1757-4676
IS - 1
ER -