生物谷报道:凋亡的细胞信号通路经典的一般认为一是胞外信号,细胞内的信号,包括线粒体信号,内质网信号通路和高尔基体信号通路三条。而它们共同的终末是caspase,但caspase导致凋亡的机理是在细胞核内和DNA damage。但是最新研究发现caspase不仅在胞浆内,而且能影响线粒体的呼吸链,它能切割线粒体呼吸链复合物I的一个75kd的亚基,从而使线粒体的呼吸功能产生抑制,进一步导致了细胞凋亡的发生。生物谷专家认为,这一研究表明,细胞凋亡的信号远比我们想象的复杂,细胞内不同的信号通路会产生交叉影响,而且凋亡相关的蛋白作用机理也比我们想象复杂,可能具有很我未知功能。
Mitochondrial outer membrane permeabilization and cytochrome c release promote caspase activation and execution of apoptosis through cleavage of specific caspase substrates in the cell. Among the first targets of activated caspases are the permeabilized mitochondria themselves, leading to disruption of electron transport, loss of mitochondrial transmembrane potential (Δm), decline in ATP levels, production of reactive oxygen species (ROS), and loss of mitochondrial structural integrity.
Here, we identify NDUFS1, the 75 kDa subunit of respiratory complex I, as a critical caspase substrate in the mitochondria. Cells expressing a noncleavable mutant of p75 sustain Δm and ATP levels during apoptosis, and ROS production in response to apoptotic stimuli is dampened. While cytochrome c release and DNA fragmentation are unaffected by the noncleavable p75 mutant, mitochondrial morphology of dying cells is maintained, and loss of plasma membrane integrity is delayed. Therefore, caspase cleavage of NDUFS1 is required for several mitochondrial changes associated with apoptosis.