Atg17 regulates the magnitude of the autophagic response

Atg17 regulates the magnitude of the autophagic response
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DOI:
10.1091/mbc.e04-10-0894
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发表时间:
2005-07-01
影响因子:
3.3
通讯作者:
Klionsky, DJ
Klionsky, DJ
中科院分区:
生物学3区
文献类型:
--
作者:
Cheong, H;Yorimitsu, T;Klionsky, DJ

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自噬是真核细胞用于降解和再循环胞质蛋白和过量或有缺陷的细胞器的分解代谢过程。在酵母中,自噬主要是对营养限制的反应,而在高等真核生物中,自噬也在发育过程中发挥作用。由于其本质上无限的降解能力,调节机制来调节自噬反应的时间和幅度至关重要。似乎在这方面起作用的一组蛋白质包括一种含有Atg1激酶的复合物。除了Atg1外,该复合体中的蛋白质主要参与非特异性自噬或特定类型的自噬,包括在营养生长条件下运行的细胞质到液泡靶向途径和过氧化物酶体降解。因此,这些蛋白质是调节这些途径之间转换的主要候选因子,包括隔离囊泡大小的变化,最明显的形态差异。atg17突变体形成数量减少的小自噬体。因此,它在过氧化物酶体降解方面存在缺陷,在自噬方面存在部分缺陷。Atg17通过两个线圈结构域与Atg1和Atg13相互作用,这些相互作用促进其包含在Atg1复合体中。
Autophagy is a catabolic process used by eukaryotic cells for the degradation and recycling of cytosolic proteins and excess or defective organelles. In yeast, autophagy is primarily a response to nutrient limitation, whereas in higher eukaryotes it also plays a role in developmental processes. Due to its essentially unlimited degradative capacity, it is critical that regulatory mechanisms are in place to modulate the timing and magnitude of the autophagic response. One set of proteins that seems to function in this regard includes a complex that contains the Atg1 kinase. Aside from Atg1, the proteins in this complex participate primarily in either nonspecific autophagy or specific types of autophagy, including the cytoplasm to vacuole targeting pathway, which operates under vegetative growth conditions, and peroxisome degradation. Accordingly, these proteins are prime candidates for factors that regulate the conversion between these pathways, including the change in size of the sequestering vesicle, the most obvious morphological difference. The atg17 mutant forms a reduced number of small autophagosomes. As a result, it is defective in peroxisome degradation and is partially defective for autophagy. Atg17 interacts with both Atg1 and Atg13, via two coiled-coil domains, and these interactions facilitate its inclusion in the Atg1 complex.