2026-04-18T03:31:10Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/200322024-09-27T09:26:05Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2024-02 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. 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 An ETFDH-driven metabolon supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis.