| 11527970 |
Chauvin C, De Oliveira F, Ronot X, Mousseau M, Leverve X, Fontaine E: Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells. J Biol Chem. 2001 Nov 2;276(44):41394-8. Epub 2001 Aug 29.
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. |
31(0,1,1,1) |