Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Germany.
Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Germany.
FEBS J. 2022 Jan;289(1):75-89. doi: 10.1111/febs.15824. Epub 2021 Apr 5.
Autophagy is a highly conserved catabolic process cells use to maintain their homeostasis by degrading misfolded, damaged and excessive proteins, nonfunctional organelles, foreign pathogens and other cellular components. Hence, autophagy can be nonselective, where bulky portions of the cytoplasm are degraded upon stress, or a highly selective process, where preselected cellular components are degraded. To distinguish between different cellular components, autophagy employs selective autophagy receptors, which will link the cargo to the autophagy machinery, thereby sequestering it in the autophagosome for its subsequent degradation in the lysosome. Autophagy receptors undergo post-translational and structural modifications to fulfil their role in autophagy, or upon executing their role, for their own degradation. We highlight the four most prominent protein modifications - phosphorylation, ubiquitination, acetylation and oligomerisation - that are essential for autophagy receptor recruitment, function and turnover. Understanding the regulation of selective autophagy receptors will provide deeper insights into the pathway and open up potential therapeutic avenues.
自噬是一种高度保守的分解代谢过程，细胞通过降解错误折叠、受损和过量的蛋白质、功能失调的细胞器、外来病原体和其他细胞成分来维持自身的内稳态。因此，自噬可以是非选择性的，在应激时降解大量细胞质；也可以是高度选择性的，降解预先选定的细胞成分。为了区分不同的细胞成分，自噬利用选择性自噬受体，将货物与自噬机制连接起来，从而将其隔离在自噬体中，随后在溶酶体中降解。自噬受体经历翻译后和结构修饰，以发挥其在自噬中的作用，或者在执行其作用后，自身降解。我们强调了四种最突出的蛋白质修饰——磷酸化、泛素化、乙酰化和寡聚化，它们对于自噬受体的招募、功能和周转至关重要。深入了解选择性自噬受体的调控将为该途径提供更深入的见解，并开辟潜在的治疗途径。
