The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency

Adela Guarás, Ester Perales-Clemente, Enrique Calvo, Rebeca Acín-Pérez, Marta Loureiro-Lopez, Claire Pujol, Isabel Martínez-Carrascoso, Estefanía Nuñez, Fernando García-Marqués, María Angeles Rodríguez-Hernández, Ana Cortés, Francisca Diaz, Acisclo Pérez-Martos, Carlos T. Moraes, Patricio Fernández-Silva, Aleksandra Trifunovic, Plácido Navas, Jesús Vazquez, Jose A. Enríquez

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)197-209
Number of pages13
JournalCell Reports
Volume15
Issue number1
DOIs
StatePublished - Apr 5 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Guarás, A., Perales-Clemente, E., Calvo, E., Acín-Pérez, R., Loureiro-Lopez, M., Pujol, C., Martínez-Carrascoso, I., Nuñez, E., García-Marqués, F., Rodríguez-Hernández, M. A., Cortés, A., Diaz, F., Pérez-Martos, A., Moraes, C. T., Fernández-Silva, P., Trifunovic, A., Navas, P., Vazquez, J., & Enríquez, J. A. (2016). The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency. Cell Reports, 15(1), 197-209. https://doi.org/10.1016/j.celrep.2016.03.009