Autophagy is required for necrotic cell death in Caenorhabditis elegans
Autophagy is required for necrotic cell death in Caenorhabditis elegans
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DOI：
10.1038/sj.cdd.4402231
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发表时间：
2008-01-01
影响因子：
12.4
通讯作者：
Tavernarakis, N.
中科院分区：
文献类型：
--
作者：
Samara, C.;Syntichaki, P.;Tavernarakis, N.
自噬是细胞在细胞内或细胞外应激下进行蛋白质和细胞器循环的主要过程。自噬的失调与诸如癌症、肌肉疾病和神经变性的病理状况有关。坏死性细胞死亡是急性神经退行性事件如缺血性卒中中广泛神经元丢失的基础。我们发现在C.优美的此外，自噬是坏死细胞死亡所必需的。通过自噬基因的遗传失活或通过药物治疗来削弱自噬抑制坏死。自噬与溶酶体分解代谢机制协同促进细胞死亡。我们的研究结果表明，自噬有助于坏死过程中的细胞破坏。因此，干扰自噬过程可以保护人类神经元免受坏死损伤。
Autophagy is the main process for bulk protein and organelle recycling in cells under extracellular or intracellular stress. Deregulation of autophagy has been associated with pathological conditions such as cancer, muscular disorders and neurodegeneration. Necrotic cell death underlies extensive neuronal loss in acute neurodegenerative episodes such as ischemic stroke. We find that excessive autophagosome formation is induced early during necrotic cell death in C. elegans. In addition, autophagy is required for necrotic cell death. Impairment of autophagy by genetic inactivation of autophagy genes or by pharmacological treatment suppresses necrosis. Autophagy synergizes with lysosomal catabolic mechanisms to facilitate cell death. Our findings demonstrate that autophagy contributes to cellular destruction during necrosis. Thus, interfering with the autophagic process may protect neurons against necrotic damage in humans.