Autophagy, not apoptosis, is essential for midgut cell death in Drosophila.
Autophagy, not apoptosis, is essential for midgut cell death in Drosophila.
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DOI：
10.1016/j.cub.2009.08.042
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发表时间：
2009-11-03
期刊：
影响因子：
--
通讯作者：
Kumar S
中科院分区：
文献类型：
--
作者：
Denton D;Shravage B;Simin R;Mills K;Berry DL;Baehrecke EH;Kumar S
后生动物中大多数发育程序性细胞死亡是由半胱天冬酶介导的。在果蝇的蜕变过程中，过时的组织，包括中肠和唾液腺，通过程序性细胞死亡被移除。引发剂caspase Dronc及其激活剂Ark是唾液腺死亡所必需的，但不是中肠移除所必需的。除了半胱天酶，唾液腺的完全清除需要自噬。然而，自噬在中肠细胞死亡中的作用尚未被探讨。对主要启动剂和效应剂半胱天冬酶的联合突变体的检查显示，典型的凋亡途径不是中肠细胞死亡所必需的。进一步的分析表明，caspase衰变是死亡中肠中caspase活性的主要原因，但抑制该活性对中肠移除没有影响。相比之下，自噬抑制严重延缓了中肠降解，而caspase活性并未降低。令人惊讶的是，半胱天冬酶和自噬的联合抑制并没有导致中肠切除的额外延迟。总之，我们的研究结果表明，自噬，而不是caspase，是中肠程序性细胞死亡所必需的，这提供了第一个体内证据，证明尽管存在高caspase活性，但caspase独立的程序性细胞死亡需要自噬。
Most developmentally programmed cell death in metazoans is mediated by caspases. During Drosophila metamorphosis obsolete tissues, including the midgut and salivary glands, are removed by programmed cell death. The initiator caspase Dronc and its activator Ark are required for the death of salivary glands, but not for midgut removal. In addition to caspases, complete removal of salivary glands requires autophagy. However, the contribution of autophagy to midgut cell death has not been explored. Examination of combined mutants of the main initiator and effector caspases revealed that the canonical apoptotic pathway is not required for midgut cell death. Further analyses revealed that the caspase Decay is responsible for most of the caspase activity in dying midguts, yet inhibition of this activity has no effect on midgut removal. By contrast, midgut degradation was severely delayed by inhibition of autophagy, and this occurred without a decrease in caspase activity. Surprisingly, the combined inhibition of caspases and autophagy did not result in an additional delay in midgut removal. Together, our results indicate that autophagy, not caspases, is essential for midgut programmed cell death, providing the first in vivo evidence of caspase-independent programmed cell death that requires autophagy, despite the presence of high caspase activity.
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