Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells. - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2001

Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells.

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Abstract

The permeability transition pore (PTP) is a mitochondrial inner membrane Ca(2+)-sensitive channel that plays a key role in different models of cell death. Because functional links between the PTP and the respiratory chain complex I have been reported, we have investigated the effects of rotenone on PTP regulation in U937 and KB cells. We show that rotenone was more potent than cyclosporin A at inhibiting Ca(2+)-induced PTP opening in digitonin-permeabilized cells energized with succinate. Consistent with PTP regulation by electron flux through complex I, the effect of rotenone persisted after oxidation of pyridine nucleotides by duroquinone. tert-butyl hydroperoxide induced PTP opening in intact cells (as shown by mitochondrial permeabilization to calcein and cobalt), as well as cytochrome c release and cell death. All these events were prevented by rotenone or cyclosporin A. These data demonstrate that respiratory chain complex I plays a key role in PTP regulation in vivo and confirm the importance of PTP opening in the commitment to cell death.

Dates and versions

inserm-00389984 , version 1 (30-05-2009)

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Christiane Chauvin, Frédéric de Oliveira, Xavier Ronot, Mireille Mousseau, Xavier M Leverve, et al.. Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells.. Journal of Biological Chemistry, 2001, 276 (44), pp.41394-8. ⟨10.1074/jbc.M106417200⟩. ⟨inserm-00389984⟩
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