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Journal Articles Journal of Bioenergetics Year : 2006

The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin.

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Abstract

Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory chain complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Delta Phi(m)), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate-malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate-malate. Moreover, while rotenone both increased and decreased ROS production at complex 1 depending on forward (glutamate-malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

Dates and versions

inserm-00388702 , version 1 (27-05-2009)

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Cécile Batandier, Bruno Guigas, Dominique Detaille, M-Yehia El-Mir, Eric M. Fontaine, et al.. The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin.. Journal of Bioenergetics, 2006, 38 (1), pp.33-42. ⟨10.1007/s10863-006-9003-8⟩. ⟨inserm-00388702⟩

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