Gogvadze Vladimir, Zhivotovsky Boris
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
J Bioenerg Biomembr. 2007 Feb;39(1):23-30. doi: 10.1007/s10863-006-9054-x.
Stimulation of cell death is a powerful instrument in the organism's struggle with cancer. Apoptosis represents one mode of cell death. However, in a variety of tumor cells proapoptotic mechanisms are downregulated, or not properly activated, whereas antiapoptotic mechanisms are upregulated. Mitochondria are known as key players in the regulation of apoptotic pathways. Specifically, permeabilization of the mitochondrial outer membrane and subsequent release of proapoptotic proteins from the intermembrane space are viewed as decisive events in the initiation and/or execution of apoptosis. Disruption of mitochondrial functions by anticancer drugs, which induce oxidative stress, inhibit mitochondrial respiration, or uncouple oxidative phosphorylation, can sensitize mitochondria in these cells and facilitate outer membrane permeabilization.
刺激细胞死亡是机体对抗癌症的有力手段。细胞凋亡是细胞死亡的一种方式。然而，在多种肿瘤细胞中，促凋亡机制下调或未被适当激活，而抗凋亡机制上调。线粒体是凋亡途径调控中的关键参与者。具体而言，线粒体外膜通透性增加以及随后促凋亡蛋白从膜间隙释放被视为凋亡起始和/或执行中的决定性事件。抗癌药物通过诱导氧化应激、抑制线粒体呼吸或使氧化磷酸化解偶联来破坏线粒体功能，可使这些细胞中的线粒体敏感化并促进外膜通透性增加。
