生物谷報道：凋亡的細(xì)胞信號通路經(jīng)典的一般認(rèn)為一是胞外信號，細(xì)胞內(nèi)的信號,，包括線粒體信號,，內(nèi)質(zhì)網(wǎng)信號通路和高爾基體信號通路三條。而它們共同的終末是caspase,，但caspase導(dǎo)致凋亡的機(jī)理是在細(xì)胞核內(nèi)和DNA damage,。但是最新研究發(fā)現(xiàn)caspase不僅在胞漿內(nèi)，而且能影響線粒體的呼吸鏈,，它能切割線粒體呼吸鏈復(fù)合物I的一個75kd的亞基,，從而使線粒體的呼吸功能產(chǎn)生抑制，進(jìn)一步導(dǎo)致了細(xì)胞凋亡的發(fā)生,。生物谷專家認(rèn)為,，這一研究表明，細(xì)胞凋亡的信號遠(yuǎn)比我們想象的復(fù)雜,，細(xì)胞內(nèi)不同的信號通路會產(chǎn)生交叉影響,，而且凋亡相關(guān)的蛋白作用機(jī)理也比我們想象復(fù)雜，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.