Cheong Heesun, Yorimitsu Tomohiro, Reggiori Fulvio, Legakis Julie E, Wang Chao-Wen, Klionsky Daniel J
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Mol Biol Cell. 2005 Jul;16(7):3438-53. doi: 10.1091/mbc.e04-10-0894. Epub 2005 May 18.
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 atg17delta 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.
自噬是真核细胞用于降解和循环利用胞质蛋白以及多余或有缺陷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一种反应，而在高等真核生物中，它在发育过程中也发挥作用。由于其本质上具有无限的降解能力，因此至关重要的是要有调节机制来调控自噬反应的时间和强度。在这方面似乎发挥作用的一组蛋白质包括一个含有Atg1激酶的复合体。除了Atg1之外，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以及过氧化物酶体降解。因此，这些蛋白质是调节这些途径之间转换的因子的主要候选者，包括隔离小泡大小的变化，这是最明显的形态学差异。atg17δ突变体形成的小自噬体数量减少。因此，它在过氧化物酶体降解方面存在缺陷，并且在自噬方面部分存在缺陷。Atg17通过两个卷曲螺旋结构域与Atg1和Atg13相互作用，这些相互作用促进其被纳入Atg1复合体。
