Department of Medical Genetics, University of Cambridge, Cambridge, UK.
UK Dementia Research Institute, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.
Exp Mol Med. 2021 Jan;53(1):30-41. doi: 10.1038/s12276-021-00556-4. Epub 2021 Jan 22.
Posttranslational modifications of proteins, such as acetylation, are essential for the regulation of diverse physiological processes, including metabolism, development and aging. Autophagy is an evolutionarily conserved catabolic process that involves the highly regulated sequestration of intracytoplasmic contents in double-membrane vesicles called autophagosomes, which are subsequently degraded after fusing with lysosomes. The roles and mechanisms of acetylation in autophagy control have emerged only in the last few years. In this review, we describe key molecular mechanisms by which previously identified acetyltransferases and deacetylases regulate autophagy. We highlight how p300 acetyltransferase controls mTORC1 activity to regulate autophagy under starvation and refeeding conditions in many cell types. Finally, we discuss how altered acetylation may impact various neurodegenerative diseases in which many of the causative proteins are autophagy substrates. These studies highlight some of the complexities that may need to be considered by anyone aiming to perturb acetylation under these conditions.
蛋白质的翻译后修饰，如乙酰化，对于调节多种生理过程至关重要，包括代谢、发育和衰老。自噬是一种进化上保守的分解代谢过程，涉及到细胞质内容物在双层膜囊泡（自噬体）中的高度调节性隔离，这些囊泡随后与溶酶体融合后被降解。在过去的几年中，乙酰化在自噬调控中的作用和机制才逐渐被揭示。在这篇综述中，我们描述了先前鉴定的乙酰转移酶和去乙酰化酶调节自噬的关键分子机制。我们强调了 p300 乙酰转移酶如何控制 mTORC1 活性，以在许多细胞类型中调节饥饿和再喂养条件下的自噬。最后，我们讨论了在许多自噬底物是神经退行性疾病中，乙酰化的改变如何影响这些疾病。这些研究强调了在这些条件下试图扰乱乙酰化的任何人都可能需要考虑的一些复杂性。
