2026-04-18T03:30:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/200322024-09-27T09:26:05Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Herrero Martín, Juan Cruz
author
Salegi Ansa, Beñat
author
Álvarez-Rivera, Gerardo
author
Domínguez-Zorita, Sonia
author
Rodríguez-Pombo, Pilar
author
Pérez, Belén
author
Calvo, Enrique
author
Paradela, Alberto
author
Miguez, David G
author
Cifuentes, Alejandro
author
Cuezva, José M
author
Formentini, Laura
funder
Ministerio de Ciencia e Innovación (España)
funder
Ministerio de Universidades (España)
2024-07-03T13:20:09Z
2024-07-03T13:20:09Z
2024-02
Nat Metab. 2024 Feb;6(2):209-225.
http://hdl.handle.net/20.500.12105/20032
38243131
10.1038/s42255-023-00956-y
2522-5812
Nature metabolism
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.
eng
An ETFDH-driven metabolon supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis.
journal article
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URL
https://repisalud.isciii.es/bitstreams/bacc73f2-62f1-49d1-9e5f-ed73e9cc48cf/download
File
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application/pdf
An ETFDH_driven metabolon supports_Nat Metab_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/e7270a40-73f3-46a3-ad0f-085f6538fee3/download
File
MD5
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text/plain
An ETFDH_driven metabolon supports_Nat Metab_2024.pdf.txt