Berridge Michael V, Herst Patries M, Lawen Alfons
Malaghan Institute of Medical Research, New Zealand.
Mol Nutr Food Res. 2009 Jan;53(1):76-86. doi: 10.1002/mnfr.200700493.
The past decade has seen the emergence of a new mechanistic paradigm of cancer therapeutics. Not only have mitochondria taken centre stage as key cellular organelles mediating intrinsic pathways of cell death by apoptosis, but nonapoptotic pathways have also been shown to involve mitochondrial mechanisms. Both pathways of cell death involve permeabilization of mitochondrial membranes, but the exact nature of the molecular complexes involved at the inner mitochondrial membrane (IMM) and outer mitochondrial membrane (OMM) remains uncertain in the light of recent gene knockout studies. Consequently, the boundary between mitochondrially-mediated apoptotic and nonapoptotic cell death is controversial. Here, we discuss the nature of the pore complexes involved in permeabilization of the IMM and OMM. Several compounds that interact directly with components of these pore complexes and have been shown to exhibit anticancer activity are discussed while other compounds appear to act indirectly through stress-related pathways.
在过去十年中，癌症治疗领域出现了一种新的机制范式。线粒体不仅作为介导细胞凋亡内在途径的关键细胞器成为焦点，而且非凋亡途径也已被证明涉及线粒体机制。两种细胞死亡途径都涉及线粒体膜的通透性改变，但根据最近的基因敲除研究，线粒体内膜（IMM）和线粒体外膜（OMM）所涉及的分子复合物的确切性质仍不确定。因此，线粒体介导的凋亡性和非凋亡性细胞死亡之间的界限存在争议。在此，我们讨论参与IMM和OMM通透性改变的孔复合物的性质。文中讨论了几种直接与这些孔复合物成分相互作用并已显示出抗癌活性的化合物，而其他化合物似乎通过与应激相关的途径间接发挥作用。
