Rodriguez-Hernandez 2009 Autophagy

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Rodríguez-Hernández A, Cordero MD, Salviati L, Artuch R, Pineda M, Briones P, Izquierdo LG, Cotán D, Navas P, Sánchez-Alcázar JA (2009) Coenzyme Q deficiency triggers mitochondria degradation by mitophagy. Autophagy 5:19-32.

» PMID: 19115482 Open Access

Rodriguez-Hernandez A, Cordero MD, Salviati L, Artuch R, Pineda M, Briones P, Izquierdo LG, Cotan D, Navas P, Sanchez-Alcazar JA (2009) Autophagy

Abstract: Coenzyme Q10 (CoQ) is a small lipophilic molecule critical for the transport of electrons from complexes I and II to complex III in the mitochondrial respiratory chain. CoQ deficiency is a rare human genetic condition that has been associated with a variety of clinical phenotypes. With the aim of elucidating how CoQ deficiency affects an organism, we have investigated the pathophysiologic processes present within fibroblasts derived from 4 patients with CoQ deficiency. Assays of cultured fibroblasts revealed decreased activities of complex II+III, complex III, and complex IV, reduced expression of mitochondrial proteins involved in oxidative phosphorylation, decreased mitochondrial membrane potential, increased production of reactive oxygen species (ROS), activation of mitochondrial permeability transition (MPT), and reduced growth rates. These abnormalities were partially restored by CoQ supplementation. Moreover, we demonstrate that CoQ deficient fibroblasts exhibited increased levels of lysosomal markers (beta-galactosidase, cathepsin, LC3, and Lyso Tracker), and enhanced expression of autophagic genes at both transcriptional and translational levels, indicating the presence of autophagy. Electron microscopy studies confirmed a massive degradation of the altered mitochondria by mitophagy. Autophagy in CoQ deficient fibroblasts was abolished by antioxidants or cyclosporin treatments suggesting that both ROS and MPT participate in this process. Furthermore, prevention of autophagy in CoQ deficient fibroblasts by 3-methyl adenine or wortmannin, as well as the induction of CoQ deficiency in cells lacking autophagy (by means of genetic knockout of the Atg5 gene in mouse embryonic fibroblasts) resulted in apoptotic cell death, suggesting a protective role of autophagy in CoQ deficiency.

Bioblast editor: Komlodi T

Cited by

  • Komlodi et al (2021) Simultaneous measurement of respiration and redox state of the Coenzyme Q pool in mitochondrial preparations. Bioenerg Commun 2021.3 doi:10.26124/bec:2021-0003


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