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.

journal_name

J Bioenerg Biomembr

authors

Batandier C,Guigas B,Detaille D,El-Mir MY,Fontaine E,Rigoulet M,Leverve XM

doi

10.1007/s10863-006-9003-8

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

33-42

issue

1

eissn

0145-479X

issn

1573-6881

journal_volume

38

pub_type

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