活性氧、线粒体通透性转换与细胞凋亡

Reactive Oxygen Species,Mitochondrial Permeability Transition and Apoptosis

线粒体是真核细胞中非常重要的细胞器,细胞中的活性氧等自由基主要来源于此,线粒体膜的通透性转换(mitochondrial permeability transition,MPT)及其孔道(mitochondrialpermeability transition pore,MPTP)更是在内源性细胞凋亡中发挥了关键作用。持续性的线粒体膜通透性转换在凋亡的效应阶段起决定性作用,可介导细胞色素c等促凋亡因子从线粒体释放到胞浆中,进一步激活下游的信号通路,导致细胞不可逆地走向凋亡。瞬时性的线粒体膜通透性转换及其偶联的线粒体局部的活性氧爆发同样具有促凋亡的作用。线粒体通透性孔道的开放释放出大量活性氧,这些活性氧又能够进一步激活该孔道,以正反馈的形式进一步加剧孔道的打开,放大凋亡信号。活性氧、线粒体通透性转换与细胞凋亡之间具有密不可分的联系,本文根据已知的研究结果集中讨论了这三者的关系,并着重论述了该领域中的最新发现和成果。

Mitochondria constitute the main source of reactive oxygen species （ROS） in eukaryotic cells and it has been well-established that oxidative stress triggers cell death. The mitochondrial permeability transition （MPT） is crucial to many forms of apoptosis, which is also known as programmed cell death. Through integration of diverse intracellular signals, the MPT serves as a logic gate that, once switched-on, commits the cell to death. Specifically, the irreversible MPT （iMPT） causes massive release of cytochrome c and other apoptosis-inducing factors from the mitochondria into the cytoplasm, accompanied by an intense burst of ROS production. Besides this, transient MPT （tMPT） due to flickering opening of the mitochondrial permeability transition pore （MPTP） also acts as early mitochondrial signals mediating the apoptotic response during oxidative stress.