自噬蛋白乙酰化修饰在自噬膜泡形成中的功能和调控

自噬膜泡的形成是自噬发生的标志和自噬完成的基础，自噬膜泡形成研究是细胞自噬研究的重点内容。众多自噬相关蛋白需要经过翻译后修饰包括乙酰化-脱乙酰化修饰方可获得自噬活性并在自噬膜泡形成中发挥作用。我们最近的研究发现，应对不同的自噬诱导信号，自噬相关蛋白的乙酰化和脱乙酰化涉及不同的乙酰转移酶和脱乙酰化酶。本研究拟在前期研究的基础上，深入了解：(1) AMPK-GAPDH通路激活脱乙酰化酶Sirt1启动自噬的机制；(2) mTOR通过影响乙酰转移酶p300活性调控自噬膜泡的形成；(3) 乙酰转移酶p300对III型PI3K活性的调控。通过上述几方面的研究，深刻认识这些乙酰转移酶和脱乙酰化酶在自噬膜泡形成中的作用，揭示自噬信号调控这些乙酰转移酶和脱乙酰化酶活性及自噬蛋白乙酰化-脱乙酰化修饰影响其自噬活性的分子机理，从而促进对自噬膜泡形成控制机制的认识。

The biogenesis of double-membrane autophagosomes is a crucial step and the hallmark of autophagy. Understanding of the molecular mechanisms for the formation of autophagosomes is pivotal to autophagy-related studies. Accumulating data have suggested that the posttranslational modifications including acetylation-deacetylation of a number of autophagy-related proteins (Atgs) are essential for them to function in autophagosome formation. Our recent data demonstrated that in cope with different autophagic signals, distinct acetyltransferases and/or deacetylases are involved in the acetylation-deacetylations of the Atg proteins. Base on the findings, we plan to investigate in this study: (1) The mechanisms underlying the activation of the deacetylase Sirt1 and initiation of autophagy by the AMPK-GAPDH pathway; (2) Regulation of acetyltrnasferase p300 by mTOR in autophagosome formation; (3) Regulation of PI3K-III by p300. By these studies, we aim to deepen our understanding of the function of these acetyltransferase and deacetylase in autophagosome formation, clarifying the molecular mechanisms by which autophagic signaling regulates these enzymes and the acetylation-deacetylation controls Atg activities during autophagosome formation.