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Cell Rep. 2016 Apr 5;15(1):197-209. doi: 10.1016/j.celrep.2016.03.009. Epub 2016 Mar 24.

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

Author information

1
Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
2
Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
3
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
4
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, Sevilla 41013, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Sevilla 41013, Spain.
5
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
6
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza 50009, Spain.
7
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Cell Biology and Anatomy, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
8
Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza 50009, Spain. Electronic address: jaenriquez@cnic.es.

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.

PMID:
27052170
DOI:
10.1016/j.celrep.2016.03.009
[Indexed for MEDLINE]
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