Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila

Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila
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DOI:
10.1101/gad.1600707
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发表时间:
2007-12-01
影响因子:
10.5
通讯作者:
Neufeld, Thomas P.
Neufeld, Thomas P.
中科院分区:
生物学1区
文献类型:
--
作者:
Juhasz, Gabor;Erdi, Balazs;Neufeld, Thomas P.

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自噬是一种细胞质降解和再循环的细胞过程,在变态过程中诱导果蝇幼虫组织,可能有助于它们的破坏或重组。出乎意料的是,我们发现,尽管自噬存在严重缺陷,但缺乏核心自噬调控因子ATG7的果蝇是可行的。虽然变态细胞死亡在ATG7突变体中受到干扰,但幼虫-成虫中肠的转变正常进行,延长的蛹发育补偿了减少的自噬。ATG7(-/-)成体寿命短,对营养和氧化应激敏感,在退化的神经元中积累泛素阳性聚集体。因此,正常水平的自噬对于应激生存和持续的细胞更新是至关重要的,但不是变态。
Autophagy, a cellular process of cytoplasmic degradation and recycling, is induced in Drosophila larval tissues during metamorphosis, potentially contributing to their destruction or reorganization. Unexpectedly, we find that flies lacking the core autophagy regulator Atg7 are viable, despite severe defects in autophagy. Although metamorphic cell death is perturbed in Atg7 mutants, the larval-adult midgut transition proceeds normally, with extended pupal development compensating for reduced autophagy. Atg7(-/-) adults are short-lived, hypersensitive to nutrient and oxidative stress, and accumulate ubiquitin-positive aggregates in degenerating neurons. Thus, normal levels of autophagy are crucial for stress survival and continuous cellular renewal, but not metamorphosis.