Pellegrini L, Scorrano L
Centre de Recherche Universite' Laval Robert Giffard, 2601 Ch. de la Canardiere, Quebec, Canada.
Cell Death Differ. 2007 Jul;14(7):1275-84. doi: 10.1038/sj.cdd.4402145. Epub 2007 Apr 20.
Mitochondria are crucial amplifiers of death signals. They release cytochrome c and other pro-apoptotic factors required to fully activate effector caspases. This release is accompanied by fragmentation of the mitochondrial reticulum and by remodelling of the internal structure of the organelle. Here we review data supporting the existence of a regulatory network in the inner mitochondrial membrane that includes optic atrophy 1 (Opa1), a dynamin-related protein, and presenilin-associated rhomboid-like (Parl), a rhomboid protease. Opa1 regulates remodelling of the cristae independent of its effect on fusion. Cristae remodelling conversely requires Parl, which participates in the production of a soluble form of Opa1 retrieved together with the integral membrane one in oligomers that are disrupted early during apoptosis. Parl itself is regulated by proteolysis to generate a cleaved form, which in turn modulates the shape of the mitochondrial reticulum. Cleavage of Parl depends on its phosphorylation state around the cleavage site, implicating mitochondrial kinases and phosphatases in the regulation of mitochondrial shape.
线粒体是死亡信号的关键放大器。它们释放细胞色素c和其他完全激活效应半胱天冬酶所需的促凋亡因子。这种释放伴随着线粒体网状结构的碎片化以及细胞器内部结构的重塑。在此，我们综述了支持线粒体内膜中存在一个调控网络的数据，该网络包括一种与发动蛋白相关的蛋白视神经萎缩蛋白1（Opa1）和一种菱形蛋白酶早老素相关类菱形蛋白（Parl）。Opa1独立于其对融合的影响来调节嵴的重塑。相反，嵴的重塑需要Parl，Parl参与产生一种可溶性形式的Opa1，该形式与整合膜形式的Opa1一起存在于凋亡早期被破坏的寡聚体中。Parl自身受蛋白水解调控以产生一种裂解形式，进而调节线粒体网状结构的形状。Parl的裂解取决于其裂解位点周围的磷酸化状态，这表明线粒体激酶和磷酸酶参与了线粒体形状的调控。
