摘要：

We and others have recently shown that loss of the mitochondrial membrane potential (螖蠄) precedes apoptosis and chemical-hypoxia-induced necrosis and is prevented by Bcl-2. In this report, we examine the biochemical mechanism used by Bcl-2 to prevent 螖蠄 loss, as determined with mitochondria isolated from a cell line overexpressing human Bcl-2 or from livers of Bcl-2 transgenic mice. Although Bcl-2 had no effect on the respiration rate of isolated mitochondria, it prevented both 螖蠄 loss and the permeability transition (PT) induced by various reagents, including Ca, HO, and -butyl hydroperoxide. Even under conditions that did not allow PT, Bcl-2 maintained 螖蠄, suggesting that the functional target of Bcl-2 is regulation of 螖蠄 but not PT. Bcl-2 also maintained 螖蠄 in the presence of the protonophore SF6847, which induces proton influx, suggesting that Bcl-2 regulates ion transport to maintain 螖蠄. Although treatment with SF6847 in the absence of Cacaused massive Hinflux in control mitochondria, the presence of Bcl-2 induced Hefflux after transient Hinflux. In this case, Bcl-2 did not enhance Kefflux. Furthermore, Bcl-2 enhanced Hefflux but not Kflux after treatment of mitochondria with Caor -butyl hydroperoxide. These results suggest that Bcl-2 maintains 螖蠄 by enhancing Hefflux in the presence of 螖蠄-loss-inducing stimuli.

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