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The ROS Production Induced by a Reverse-Electron Flux at Respiratory-Chain Complex 1 is Hampered by Metformin
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.
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“inhibition of mitochondrial complex 1 in the electron transport chain and reduction of endogenous production of reactive oxygen species (ROS) (Batandier et al., 2006; Bridges et al., 2014; Zheng et al., 2012)”
From Metformin as a tool to target aging (2016) · cites this paper as Batandier et al., 2006
In the citing paper
“inhibition of mitochondrial complex 1 in the electron transport chain and reduction of endogenous production of reactive oxygen species (ROS) (Batandier et al., 2006; Bridges et al., 2014; Zheng et al., 2012)”
From Metformin as a tool to target aging (2016) · cites this paper as Batandier et al., 2006
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Metadata
- Authors
- Batandier, C., Guigas, B., Detaille, D., El-Mir, M., Fontaine, E., Rigoulet, M., & Leverve, X. M.
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2006-02
- Volume
- 38
- Issue
- 1
- Pages
- 33-42
- ISSN
- 0145-479X
- 1573-6881
- Cited by
- 279
- References
- 7
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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