The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis

作者：Ruth M. Kluck, Ella Bossy‐Wetzel, Douglas R. Green, Donald D. Newmeyer · 发表于：Science · 年份：1997 · 被引用次数：4752 · 研究领域：Cell death mechanisms and regulation、Mitochondrial Function and Pathology、Autophagy in Disease and Therapy

In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology. Bcl-2 acted in situ on mitochondria to prevent the release of cytochrome c and thus caspase activation. During apoptosis in intact cells, cytochrome c translocation was similarly blocked by Bcl-2 but not by a caspase inhibitor, zVAD-fmk. In vitro, exogenous cytochrome c bypassed the inhibitory effect of Bcl-2. Cytochrome c release was unaccompanied by changes in mitochondrial membrane potential. Thus, Bcl-2 acts to inhibit cytochrome c translocation, thereby blocking caspase activation and the apoptotic process.