| First Author | Herrero Martín JC | Year | 2024 |
| Journal | Nat Metab | Volume | 6 |
| Issue | 2 | Pages | 209-225 |
| PubMed ID | 38243131 | Mgi Jnum | J:345923 |
| Mgi Id | MGI:7610106 | Doi | 10.1038/s42255-023-00956-y |
| Citation | Herrero Martin JC, et al. (2024) An ETFDH-driven metabolon supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis. Nat Metab 6(2):209-225 |
| abstractText | 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 (QH(2)); however, in eukaryotes, only oxidative phosphorylation (OXPHOS) complex III (CIII) oxidizes QH(2) 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 QH(2)-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. |
