Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109.
Proc Natl Acad Sci U S A. 2021 Jan 5;118(1). doi: 10.1073/pnas.2005539118.
Macroautophagy/autophagy is a highly conserved eukaryotic molecular process that facilitates the recycling of superfluous cytoplasmic materials, damaged organelles, and invading pathogens, resulting in proper cellular homeostasis and survival during stress conditions. Autophagy is stringently regulated at multiple stages, including control at transcriptional, translational, and posttranslational levels. In this work, we identified a mechanism by which regulation of autophagy is achieved through the posttranslational modification of Atg9. Here, we show that, in order to limit autophagy to a low, basal level during normal conditions, Atg9 is ubiquitinated and subsequently targeted for degradation in a proteasome-dependent manner through the action of the E3 ligase Met30. When cells require increased autophagy flux to respond to nutrient deprivation, the proteolysis of Atg9 is significantly reduced. Overall, this work reveals an additional layer of mechanistic regulation that allows cells to further maintain appropriate levels of autophagy and to rapidly induce this process in response to stress.
自噬是一种高度保守的真核生物分子过程，有助于回收多余的细胞质物质、受损的细胞器和入侵的病原体，从而在应激条件下实现适当的细胞内稳态和存活。自噬在多个阶段受到严格调控，包括转录、翻译和翻译后水平的控制。在这项工作中，我们确定了一种通过翻译后修饰 Atg9 来实现自噬调控的机制。在这里，我们表明，为了在正常条件下将自噬限制在低基础水平，Atg9 被泛素化，随后通过 E3 连接酶 Met30 的作用，以蛋白酶体依赖的方式靶向降解。当细胞需要增加自噬通量来响应营养缺乏时，Atg9 的蛋白水解显著减少。总的来说，这项工作揭示了一种额外的机制调控层，使细胞能够进一步维持适当的自噬水平，并在应激时迅速诱导这一过程。
