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Régulation du Pore de Transition de Perméabilité mitochondrial et toxicité induite par les analogues de l'ubiquinone dans les hépatocytes cancéreux.

Abstract : Mitochondria play a key role in apoptotic and necrotic cell death. One of the key mitochondrial events leading to cell death is the Mitochondrial Permeability Transition (MPT), a highly regulated phenomenon mediated by an inner membrane channel opening. In rat liver mitochondria, ubiquinone analogs have showed their ability to modulate pore opening by three functional ways: activation, inhibition and inactive interaction. Although MPT inhibitors usually protect from cell death, unexpected toxicity from inhibiting ubiquinone has been reported in different cell lines.
In this work, we aimed at understanding this opposite effects using immortalized and cancerous hepatocyte cell lines. We observed that MPT regulation by ubiquinone analogs might dramatically change after immortalization or transformation into cancer, whereas the effect of cyclosporin A remained unaffected. Studies on cell cultures and co-cultures shown that this unique characteristic can lead to a selective toxicity on similar cells, depending on their status (cancer vs. immortalization). Some inhibiting ubiquinones were cytotoxic in cells where they induced a dramatic oxidative stress, whereas they were non toxic for cells where they did not affect free radical production. These findings open new perspectives in the use of MPT as a molecular targeted in cell death therapies.
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https://tel.archives-ouvertes.fr/tel-00347922
Contributor : Flavien Devun <>
Submitted on : Wednesday, December 17, 2008 - 10:29:28 AM
Last modification on : Thursday, November 19, 2020 - 3:52:36 PM
Long-term archiving on: : Tuesday, June 8, 2010 - 4:31:10 PM

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  • HAL Id : tel-00347922, version 1

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Flavien Devun. Régulation du Pore de Transition de Perméabilité mitochondrial et toxicité induite par les analogues de l'ubiquinone dans les hépatocytes cancéreux.. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2008. Français. ⟨tel-00347922⟩

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