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Theses

Voies de régulation de la fonction mitochondriale dans les modèles de tumeurs thyroïdiennes

Abstract : The main source of energy in the cell derives from the mitochondria through the oxidative phosphorylation process involving proteins coded by both nuclear and mitochondrial genomes. The transcriptional coordination of these genomes is necessary for the biogenesis of functional mitochondria, and is managed by several transcription factors, such as NRFs (Nuclear Respiratory Factors) and ERRs (Estrogen-Related Receptors). Their transcriptional efficiency is controlled by the coactivators of the PGC-1 (Peroxisome proliferator-activated receptor γ Coactivator-1) family – PGC-1α, PGC-1β and PRC (PGC-1-Related Coactivator) – their expression depending on endogenous or environmental signals. In order to specify the role of PRC in the nucleo-mitochondrial crosstalk, we used several cellular models of human follicular thyroid carcinomas (RO82 W-1, FTC-133 and XTC.UC1) presenting different mitochondrial richness, metabolic orientation and expression level for PRC and PGC-1α. This work highlighted the key role of the ERRα–PRC complex in the biogenesis of functional mitochondria. Moreover, PRC seems to coordinate cellular cycle phases with the efficiency of mitochondrial energetic metabolism and the cellular redox status. In these models, our work pointed out a role for nitric oxide and calcium as regulators of the PRC-dependent mitochondrial biogenesis and function. All these data suggest that PRC coactivator and its regulating pathways could be potential therapeutic targets for solid tumors.
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https://tel.archives-ouvertes.fr/tel-00541313
Contributor : Anne-Marie Plé <>
Submitted on : Tuesday, November 30, 2010 - 12:40:53 PM
Last modification on : Tuesday, May 7, 2019 - 6:30:13 PM
Long-term archiving on: : Tuesday, March 1, 2011 - 2:49:54 AM

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  • HAL Id : tel-00541313, version 1

Citation

S. Le Pennec. Voies de régulation de la fonction mitochondriale dans les modèles de tumeurs thyroïdiennes. Sciences du Vivant [q-bio]. Université d'Angers, 2010. Français. ⟨tel-00541313⟩

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