Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/5240
The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency
Guaras, Adela CNIC | Perales-Clemente, Ester CNIC | Calvo, Enrique CNIC | Acin-Perez, Rebeca CNIC | Loureiro, Marta CNIC | Pujol, Claire | Martinez-Carrascoso, Isabel CNIC | Nunez, Estefania CNIC | Garcia-Marques, Fernando CNIC | Angeles Rodriguez-Hernandez, Maria | Cortes, Ana | Diaz, Francisca | Perez-Martos, Acisclo | Moraes, Carlos T. | Fernandez-Silva, Patricio | Trifunovic, Aleksandra | Navas, Placido | Vazquez, Jesus CNIC | Enriquez, José Antonio CNIC
Cell Rep. 2016; 15(1):197-209
Electrons feed into the mitochondrial electron transport chain (mETC) from NAD-or FAD-dependent enzymes. A shift from glucose to fatty acids increases electron flux through FAD, which can saturate the oxidation capacity of the dedicated coenzyme Q (CoQ) pool and result in the generation of reactive oxygen species. To prevent this, the mETC superstructure can be reconfigured through the degradation of respiratory complex I, liberating associated complex III to increase electron flux via FAD at the expense of NAD. Here, we demonstrate that this adaptation is driven by the ratio of reduced to oxidized CoQ. Saturation of CoQ oxidation capacity induces reverse electron transport from reduced CoQ to complex I, and the resulting local generation of superoxide oxidizes specific complex I proteins, triggering their degradation and the disintegration of the complex. Thus, CoQ redox status acts as a metabolic sensor that fine-tunes mETC configuration in order to match the prevailing substrate profile.
ELECTRON-TRANSPORT CHAIN | MITOCHONDRIAL COMPLEX I | CYTOCHROME-C-OXIDASE | MAMMALIAN MITOCHONDRIA | SUPRAMOLECULAR ORGANIZATION | MOUSE FIBROBLASTS | B GENE | ASSEMBLY/STABILITY | SUPERCOMPLEXES | PHOSPHORYLATION
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