dc.contributor.author | Herrero Martín, Juan Cruz | |
dc.contributor.author | Salegi Ansa, Beñat | |
dc.contributor.author | Álvarez-Rivera, Gerardo | |
dc.contributor.author | Domínguez-Zorita, Sonia | |
dc.contributor.author | Rodríguez-Pombo, Pilar | |
dc.contributor.author | Pérez, Belén | |
dc.contributor.author | Calvo, Enrique | |
dc.contributor.author | Paradela, Alberto | |
dc.contributor.author | Miguez, David G | |
dc.contributor.author | Cifuentes, Alejandro | |
dc.contributor.author | Cuezva, José M | |
dc.contributor.author | Formentini, Laura | |
dc.date.accessioned | 2024-07-03T13:20:09Z | |
dc.date.available | 2024-07-03T13:20:09Z | |
dc.date.issued | 2024-02 | |
dc.identifier.citation | Nat Metab. 2024 Feb;6(2):209-225. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20032 | |
dc.description.abstract | Coenzyme Q (Q) is a key lipid electron transporter, but several aspects of its biosynthesis and redox homeostasis remain undefined. Various flavoproteins reduce ubiquinone (oxidized form of Q) to ubiquinol (QH2); however, in eukaryotes, only oxidative phosphorylation (OXPHOS) complex III (CIII) oxidizes QH2 to Q. The mechanism of action of CIII is still debated. Herein, we show that the Q reductase electron-transfer flavoprotein dehydrogenase (ETFDH) is essential for CIII activity in skeletal muscle. We identify a complex (comprising ETFDH, CIII and the Q-biosynthesis regulator COQ2) that directs electrons from lipid substrates to the respiratory chain, thereby reducing electron leaks and reactive oxygen species production. This metabolon maintains total Q levels, minimizes QH2-reductive stress and improves OXPHOS efficiency. Muscle-specific Etfdh-/- mice develop myopathy due to CIII dysfunction, indicating that ETFDH is a required OXPHOS component and a potential therapeutic target for mitochondrial redox medicine. | es_ES |
dc.description.sponsorship | We acknowledge all CBMSO (Centre for Molecular Biology Severo
Ochoa, CSIC–UAM) facilities and D. Abia from CBMSO-Bioinformatics
Unit for help and advice. We are grateful to L. Civettini for assistance
and technical discussions. Mutated ACAD9- and AOX-expressing
fibroblasts were kindly gifted by M.A. Martín-Casanueva and J.A.
Enriquez, respectively. This work was supported by grants from the
Ministerio de Ciencia e Innovación, Spain (PID2019-104241RB-I00 and
PID2022-136738OB-I00, MCIN/AEI/10.13039/501100011033) and the
Fundación Ramón Areces, Spain. Principal investigator: L.F. B.S.A. is
supported by a FPU predoctoral grant (FPU2022/00218) and G.Á.-R.
is supported by a Juan de la Cierva-Incorporación postdoctoral grant
(IJC2019-041482-I), awarded by the Ministerio de Universidades (MU)
and the Ministerio de Ciencia e Innovación (MC), respectively. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Electron-Transferring Flavoproteins | es_ES |
dc.subject.mesh | Oxidative Phosphorylation | es_ES |
dc.subject.mesh | Ubiquinone | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Homeostasis | es_ES |
dc.subject.mesh | Lipids | es_ES |
dc.subject.mesh | Muscle, Skeletal | es_ES |
dc.title | An ETFDH-driven metabolon supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 38243131 | es_ES |
dc.format.volume | 6 | es_ES |
dc.format.number | 2 | es_ES |
dc.format.page | 209 | es_ES |
dc.identifier.doi | 10.1038/s42255-023-00956-y | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Ministerio de Universidades (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2522-5812 | es_ES |
dc.relation.publisherversion | 10.1038/s42255-023-00956-y | es_ES |
dc.identifier.journal | Nature metabolism | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-104241RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2022-136738OB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/MCIN/AEI/10.13039/501100011033 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/FPU2022/00218 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IJC2019-041482-I | es_ES |