Journal of Bioenergetics and Biomembranes

, Volume 38, Issue 1, pp 33–42 | Cite as

The ROS Production Induced by a Reverse-Electron Flux at Respiratory-Chain Complex 1 is Hampered by Metformin

  • Cécile Batandier
  • Bruno Guigas
  • Dominique Detaille
  • M. El-Mir
  • Eric Fontaine
  • M. Rigoulet
  • X. M. Leverve
Original Paper


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 (Δ < eqid1 > 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.


Metformin ROS Oxidative phosphorylation Rat liver mitochondria Rotenone Malonate Antimycin Membrane potential 



electrical potential difference across the mitochondrial inner membrane


pH difference across the mitochondrial inner membrane




oxygen consumption rate


reactive oxygen species


free fatty acid – bovine serum albumin


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Copyright information

© Springer Science + Business Media, LLC. 2006

Authors and Affiliations

  • Cécile Batandier
    • 1
  • Bruno Guigas
    • 1
  • Dominique Detaille
    • 1
  • M. El-Mir
    • 2
  • Eric Fontaine
    • 1
  • M. Rigoulet
    • 3
  • X. M. Leverve
    • 1
    • 4
  1. 1.INSERM E-0221 Bioénergétique Fondamentale et AppliquéeUniversit Joseph FourierGrenobleFrance
  2. 2.Faculty of Pharmacy, Department of Physiology and PharmacologyUniversity of SalamancaSalamancaSpain
  3. 3.Institut de Biochimie et de Génétique Cellulaire de CNRSUniversit de Bordeaux IIBordeaux CedexFrance
  4. 4.Bioénergétique Fondamentale et Appliquée INSERM E-0221Universit Joseph FourierGrenoble CedexFrance

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