Open AccessCoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome
Author(s) -
LunaSánchez Marta,
HidalgoGutiérrez Agustín,
Hildebrandt Tatjana M,
ChavesSerrano Julio,
BarriocanalCasado Eliana,
SantosFandila Ángela,
Romero Miguel,
Sayed Ramy KA,
Duarte Juan,
Prokisch Holger,
Schuelke Markus,
Distelmaier Felix,
Escames Germaine,
AcuñaCastroviejo Darío,
López Luis C
Publication year - 2017
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201606345
Subject(s) - sulfurtransferase , mitochondrion , chemistry , biochemistry , thiosulfate , sulfite oxidase , endocrinology , biology , enzyme , sulfur , organic chemistry , cysteine
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 Coq9 R239X 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.