Perfettini Jean-Luc, Roumier Thomas, Kroemer Guido
Centre National de la Recherche Scientifique, UMR 8125, Institut Gustave Roussy, F-94805 Villejuif, France.
Trends Cell Biol. 2005 Apr;15(4):179-83. doi: 10.1016/j.tcb.2005.02.005.
Mitochondrial outer membrane permeabilization (MOMP) determines the point-of-no-return of most if not all signal-transduction cascades leading to cell death. It has been postulated that the molecular mechanism leading to MOMP could depend on the activation of the mitochondrial fission machinery mediated by proteins from the dynamin superfamily. However, recent work suggests that, depending on the specific apoptosis induction pathway, mitochondrial fission can occur independently or downstream from MOMP. Moreover, fragmentation of the mitochondrial network can inhibit MOMP and apoptosis in response to a particular range of lethal stimuli, namely those relying on Ca(2+) waves. Failure to transmit the Ca(2+) wave through disconnected mitochondria then interrupts the propagation of the pro-apoptotic signal. Thus, mitochondrial fission can either enhance or reduce the probability of MOMP and consequent cell death, depending on the initial lethal stimulus.
线粒体外膜通透性改变（MOMP）决定了大多数（即便不是全部）导致细胞死亡的信号转导级联反应的不可逆点。据推测，导致MOMP的分子机制可能取决于由发动蛋白超家族的蛋白质介导的线粒体分裂机制的激活。然而，最近的研究表明，根据特定的凋亡诱导途径，线粒体分裂可以独立发生，也可以发生在MOMP之后。此外，线粒体网络的碎片化可以抑制MOMP和凋亡，以应对特定范围的致死性刺激，即那些依赖于Ca(2+)波的刺激。无法通过断开连接的线粒体传递Ca(2+)波会中断促凋亡信号的传播。因此，根据初始致死性刺激的不同，线粒体分裂既可以增加也可以降低MOMP及随后细胞死亡的概率。
