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Article Dans Une Revue Cells Année : 2020

ANT2-Mediated ATP Import into Mitochondria Protects against Hypoxia Lethal Injury

Résumé

Following a prolonged exposure to hypoxia-reoxygenation, a partial disruption of the ER-mitochondria tethering by mitofusin 2 (MFN2) knock-down decreases the Ca 2+ transfer between the two organelles limits mitochondrial Ca 2+ overload and prevents the Ca 2+-dependent opening of the mitochondrial permeability transition pore, i.e., limits cardiomyocyte cell death. The impact of the metabolic changes resulting from the alteration of this Ca 2+ crosstalk on the tolerance to hypoxia-reoxygenation injury remains partial and fragmented between different field of expertise. >In this study, we report that MFN2 loss of function results in a metabolic switch driven by major modifications in energy production by mitochondria. During hypoxia, mitochondria maintain their ATP concentration and, concomitantly, the inner membrane potential by importing cytosolic ATP into mitochondria through an overexpressed ANT2 protein and by decreasing the expression and activity of the ATP hydrolase via IF1. This adaptation further blunts the detrimental hyperpolarisation of the inner mitochondrial membrane (IMM) upon re-oxygenation. These metabolic changes play an important role to attenuate cell death during a prolonged hypoxia-reoxygenation challenge.
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Dates et versions

hal-03060378 , version 1 (13-12-2020)

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Yves Gouriou, Muhammad Rizwan Alam, Zeina Harhous, Claire Crola da Silva, Delphine Baetz Baetz, et al.. ANT2-Mediated ATP Import into Mitochondria Protects against Hypoxia Lethal Injury. Cells, 2020, 9 (12), pp.2542. ⟨10.3390/cells9122542⟩. ⟨hal-03060378⟩
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