The ubiquitin-proteasome pathway (UPP) and autophagy play integral roles in cellular homeostasis. As part of their normal life cycle, most proteins undergo ubiquitination for some form of redistribution, localization and/or functional modulation. However, ubiquitination is also important to the UPP and several autophagic processes. The UPP is initiated after specific lysine residues of short-lived, damaged or misfolded proteins are conjugated to ubiquitin, which targets these proteins to proteasomes. Autophagy is the endosomal/lysosomal-dependent degradation of organelles, invading microbes, zymogen granules and macromolecules such as protein, carbohydrates and lipids. Autophagy can be broadly separated into three distinct subtypes termed microautophagy, chaperone-mediated autophagy and macroautophagy. Although autophagy was once thought of as non-selective bulk degradation, advancements in the field have led to the discovery of several selective forms of autophagy. Here, we focus on the mechanisms of primary and selective mammalian autophagy pathways and highlight the current knowledge gaps in these molecular pathways.

中文翻译：

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哺乳动物自噬的分子机制

泛素-蛋白酶体途径 (UPP) 和自噬在细胞稳态中发挥着不可或缺的作用。作为其正常生命周期的一部分，大多数蛋白质会经历泛素化以进行某种形式的重新分布、定位和/或功能调节。然而，泛素化对 UPP 和几个自噬过程也很重要。UPP 在短寿命、受损或错误折叠蛋白质的特定赖氨酸残基与泛素结合后启动，泛素将这些蛋白质靶向蛋白酶体。自噬是细胞器、入侵微生物、酶原颗粒和大分子（如蛋白质、碳水化合物和脂质）的内体/溶酶体依赖性降解。自噬可以大致分为三种不同的亚型，称为微自噬、分子伴侣介导的自噬和巨自噬。尽管自噬曾经被认为是非选择性的大量降解，但该领域的进步导致发现了几种选择性形式的自噬。在这里，我们专注于初级和选择性哺乳动物自噬途径的机制，并强调这些分子途径中当前的知识差距。