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Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I.

Abstract : We have investigated the consequences of permeability transition pore (PTP) opening on the rate of production of reactive oxygen species in isolated rat liver mitochondria. We found that PTP opening fully inhibited H(2)O(2) production when mitochondria were energized both with complex I or II substrates. Because PTP opening led to mitochondrial pyridine nucleotide depletion, H(2)O(2) production was measured again in the presence of various amounts of NADH. PTP opening-induced H(2)O(2) production began when NADH concentration was higher than 50 microm and reached a maximum at over 300 microm. At such concentrations of NADH, the maximal H(2)O(2) production was 4-fold higher than that observed when mitochondria were permeabilized with the channel-forming antibiotic alamethicin, indicating that the PTP opening-induced H(2)O(2) production was not due to antioxidant depletion. Moreover, PTP opening decreased rotenone-sensitive NADH ubiquinone reductase activity, whereas it did not affect the NADH FeCN reductase activity. We conclude that PTP opening induces a specific conformational change of complex I that (i) dramatically increases H(2)O(2) production so long as electrons are provided to complex I, and (ii) inhibits the physiological pathway of electrons inside complex I. These data allowed the identification of a novel consequence of permeability transition that may partly account for the mechanism by which PTP opening induces cell death.
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https://www.hal.inserm.fr/inserm-00389920
Contributor : Sarah Hamant <>
Submitted on : Saturday, May 30, 2009 - 11:05:23 AM
Last modification on : Friday, November 6, 2020 - 4:03:41 AM

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Cécile Batandier, Xavier Leverve, Eric Fontaine. Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2004, 279 (17), pp.17197-204. ⟨10.1074/jbc.M310329200⟩. ⟨inserm-00389920⟩

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