Kluck R M, Bossy-Wetzel E, Green D R, Newmeyer D D
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Science. 1997 Feb 21;275(5303):1132-6. doi: 10.1126/science.275.5303.1132.
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.
在无细胞凋亡系统中，线粒体自发释放细胞色素c，后者激活天冬氨酸特异性半胱氨酸蛋白酶（DEVD特异性半胱天冬酶），导致血影蛋白裂解及凋亡性核形态形成。Bcl-2在线粒体原位发挥作用，阻止细胞色素c的释放，从而防止半胱天冬酶激活。在完整细胞凋亡过程中，细胞色素c的易位同样被Bcl-2阻断，但不被半胱天冬酶抑制剂zVAD-fmk阻断。在体外，外源性细胞色素c绕过了Bcl-2的抑制作用。细胞色素c的释放并未伴随线粒体膜电位的变化。因此，Bcl-2通过抑制细胞色素c的易位来阻断半胱天冬酶激活及凋亡过程。
