Abdelwahid Eltyeb, Yokokura Takakazu, Krieser Ronald J, Balasundaram Sujatha, Fowle William H, White Kristin
Cutaneous Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
Dev Cell. 2007 May;12(5):793-806. doi: 10.1016/j.devcel.2007.04.004.
Mitochondrial disruption is a conserved aspect of apoptosis, seen in many species from mammals to nematodes. Despite significant conservation of other elements of the apoptotic pathway in Drosophila, a broad role for mitochondrial changes in apoptosis in flies remains unconfirmed. Here, we show that Drosophila mitochondria become permeable in response to the expression of Reaper and Hid, endogenous regulators of developmental apoptosis. Caspase activation in the absence of Reaper and Hid is not sufficient to permeabilize mitochondria, but caspases play a role in Reaper- and Hid-induced mitochondrial changes. Reaper and Hid rapidly localize to mitochondria, resulting in changes in mitochondrial ultrastructure. The dynamin-related protein, Drp1, is important for Reaper- and DNA-damage-induced mitochondrial disruption. Significantly, we show that inhibition of Reaper or Hid mitochondrial localization or inhibition of Drp1 significantly inhibits apoptosis, indicating a role for mitochondrial disruption in fly apoptosis.
线粒体破坏是细胞凋亡的一个保守特征，在从哺乳动物到线虫的许多物种中都能看到。尽管果蝇凋亡途径的其他元素有显著的保守性，但线粒体变化在果蝇细胞凋亡中的广泛作用仍未得到证实。在这里，我们表明，果蝇线粒体在响应发育性细胞凋亡的内源性调节因子收割者（Reaper）和隐藏者（Hid）的表达时变得通透。在没有收割者和隐藏者的情况下，半胱天冬酶激活不足以使线粒体通透，但半胱天冬酶在收割者和隐藏者诱导的线粒体变化中起作用。收割者和隐藏者迅速定位于线粒体，导致线粒体超微结构发生变化。动力蛋白相关蛋白Drp1对收割者和DNA损伤诱导的线粒体破坏很重要。重要的是，我们表明抑制收割者或隐藏者的线粒体定位或抑制Drp1可显著抑制细胞凋亡，表明线粒体破坏在果蝇细胞凋亡中起作用。
