Regulation mechanisms and signaling pathways of autophagy.

Regulation mechanisms and signaling pathways of autophagy.
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DOI:
10.1146/annurev-genet-102808-114910
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发表时间:
2009
影响因子:
11.1
通讯作者:
Klionsky DJ
Klionsky DJ
中科院分区:
生物学1区
文献类型:
--
作者:
He C;Klionsky DJ

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自噬是细胞成分的自我降解过程,其中双膜自噬体隔离细胞器或部分胞质溶胶,并与溶酶体或空泡融合以被驻留的水解酶分解。自噬响应于细胞外或细胞内应激和信号如饥饿、生长因子剥夺、ER应激和病原体感染而上调。缺陷性自噬在人类病理学中起着重要作用,包括癌症、神经变性和传染病。我们提出了我们目前的知识,在真核生物从酵母到哺乳动物细胞的自噬机制的关键基因和信号转导通路,感测不同类型的压力的状态和诱导自噬细胞的生存和稳态。我们还回顾了在不同水平上调节自噬机制的分子机制的最新进展,从转录激活到翻译后蛋白质修饰。
Autophagy is a process of self-degradation of cellular components in which double-membrane autophagosomes sequester organelles or portions of cytosol and fuse with lysosomes or vacuoles for breakdown by resident hydrolases. Autophagy is upregulated in response to extra- or intracellular stress and signals such as starvation, growth factor deprivation, ER stress, and pathogen infection. Defective autophagy plays a significant role in human pathologies, including cancer, neurodegeneration, and infectious diseases. We present our current knowledge on the key genes composing the autophagy machinery in eukaryotes from yeast to mammalian cells and the signaling pathways that sense the status of different types of stress and induce autophagy for cell survival and homeostasis. We also review the recent advances on the molecular mechanisms that regulate the autophagy machinery at various levels, from transcriptional activation to post-translational protein modification.
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