Wen Xin, Klionsky Daniel J
Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
J Mol Biol. 2016 May 8;428(9 Pt A):1681-99. doi: 10.1016/j.jmb.2016.02.021. Epub 2016 Feb 22.
Macroautophagy is an evolutionarily conserved dynamic pathway that functions primarily in a degradative manner. A basal level of macroautophagy occurs constitutively, but this process can be further induced in response to various types of stress including starvation, hypoxia and hormonal stimuli. The general principle behind macroautophagy is that cytoplasmic contents can be sequestered within a transient double-membrane organelle, an autophagosome, which subsequently fuses with a lysosome or vacuole (in mammals, or yeast and plants, respectively), allowing for degradation of the cargo followed by recycling of the resulting macromolecules. Through this basic mechanism, macroautophagy has a critical role in cellular homeostasis; however, either insufficient or excessive macroautophagy can seriously compromise cell physiology, and thus, it needs to be properly regulated. In fact, a wide range of diseases are associated with dysregulation of macroautophagy. There has been substantial progress in understanding the regulation and molecular mechanisms of macroautophagy in different organisms; however, many questions concerning some of the most fundamental aspects of macroautophagy remain unresolved. In this review, we summarize current knowledge about macroautophagy mainly in yeast, including the mechanism of autophagosome biogenesis, the function of the core macroautophagic machinery, the regulation of macroautophagy and the process of cargo recognition in selective macroautophagy, with the goal of providing insights into some of the key unanswered questions in this field.
巨自噬是一种进化上保守的动态途径，主要以降解方式发挥作用。巨自噬的基础水平是组成性发生的，但这一过程可在应对包括饥饿、缺氧和激素刺激在内的各种应激时进一步诱导。巨自噬背后的一般原理是，细胞质内容物可被隔离在一个瞬时双膜细胞器即自噬体中，自噬体随后与溶酶体或液泡（分别在哺乳动物、酵母和植物中）融合，从而使货物降解，随后对产生的大分子进行再循环利用。通过这一基本机制，巨自噬在细胞稳态中起关键作用；然而，巨自噬不足或过度都会严重损害细胞生理功能，因此，它需要得到适当调节。事实上，多种疾病都与巨自噬失调有关。在理解不同生物体中巨自噬的调控和分子机制方面已经取得了重大进展；然而，关于巨自噬一些最基本方面的许多问题仍未得到解决。在这篇综述中，我们主要总结了目前关于酵母中巨自噬的知识，包括自噬体生物发生的机制、核心巨自噬机制的功能、巨自噬的调控以及选择性巨自噬中的货物识别过程，目的是深入了解该领域一些关键的未解决问题。
