Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells
Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells
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DOI：
10.1074/jbc.m106417200
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发表时间：
2001-11-02
影响因子：
4.8
通讯作者：
Fontaine, E
中科院分区：
文献类型：
--
作者：
Chauvin, C;De Oliveira, F;Fontaine, E
The permeability transition pore (PTP) is a mitochondrial inner membrane Ca2+-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 Ca2+-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.
