A paradigm shift: AMPK negatively regulates ULK1 activity.

IF 14.6 1区 生物学 Q1 CELL BIOLOGY Autophagy Pub Date : 2024-04-01 Epub Date: 2023-06-20 DOI:10.1080/15548627.2023.2223465
Ji-Man Park, Do-Hyung Kim
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Abstract

In glucose-starved cells, macroautophagy (hereafter referred to as autophagy) is considered to serve as an energy-generating process contributing to cell survival. AMPK (adenosine monophosphate-activated protein kinase) is the primary cellular energy sensor that is activated during glucose starvation. According to the current paradigm in the field, AMPK promotes autophagy in response to energy deprivation by binding and phosphorylating ULK1 (UNC-51 like kinase 1), the protein kinase responsible for autophagy initiation. However, conflicting findings have been reported casting doubts about the current established model. In our recent study, we have thoroughly reevaluated the role of AMPK in autophagy. Contrary to the current paradigm, our study revealed that AMPK functions as a negative regulator of ULK1 activity. The study has elucidated the underlying mechanism and demonstrated the significance of the negative role in controlling autophagy and maintaining cellular resilience during energy depletion.Abbreviations: AMPK: adenosine monophosphate-activated protein kinase; ULK1: UNC-51 like kinase 1; MTORC1: mechanistic target of rapamycin complex 1; ATG14: autophagy-related protein 14; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; ATP: adenosine triphosphate; VPS34: vacuolar protein sorting 34; BECN1: Beclin 1; AMPKα: AMPK catalytic subunit α; LKB1: liver kinase B1; PIK3R4: phosphatidylinositol 3-kinase regulatory subunit 4.

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范式转变:AMPK 负向调节 ULK1 的活性。
在葡萄糖饥饿的细胞中,大自噬(以下简称自噬)被认为是一种有助于细胞存活的能量生成过程。AMPK(单磷酸腺苷激活的蛋白激酶)是葡萄糖饥饿时激活的主要细胞能量传感器。根据目前的研究范例,AMPK 通过结合并磷酸化 ULK1(UNC-51 类似激酶 1)(一种负责启动自噬的蛋白激酶)来促进自噬,以应对能量匮乏。然而,一些相互矛盾的研究结果使人们对目前已建立的模型产生了怀疑。在我们最近的研究中,我们彻底重新评估了 AMPK 在自噬中的作用。与目前的模式相反,我们的研究发现 AMPK 对 ULK1 的活性起着负向调节作用。该研究阐明了其潜在机制,并证明了其在控制自噬和维持细胞在能量耗竭时的恢复能力方面的重要作用:缩写:AMPK:单磷酸腺苷激活的蛋白激酶;ULK1:UNC-51 like kinase 1;MTORC1:雷帕霉素复合体1的机制靶标;ATG14:自噬相关蛋白14;PIK3C3:磷脂酰肌醇3-激酶催化亚基3型;ATP:三磷酸腺苷;VPS34:空泡蛋白分选34;BECN1:Beclin 1;AMPKα:LKB1:肝激酶 B1;PIK3R4:磷脂酰肌醇 3-激酶调节亚基 4。
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来源期刊
Autophagy
Autophagy 生物-细胞生物学
CiteScore
21.30
自引率
2.30%
发文量
277
审稿时长
1 months
期刊介绍: Autophagy is a peer-reviewed journal that publishes research on autophagic processes, including the lysosome/vacuole dependent degradation of intracellular material. It aims to be the premier journal in the field and covers various connections between autophagy and human health and disease, such as cancer, neurodegeneration, aging, diabetes, myopathies, and heart disease. Autophagy is interested in all experimental systems, from yeast to human. Suggestions for specialized topics are welcome. The journal accepts the following types of articles: Original research, Reviews, Technical papers, Brief Reports, Addenda, Letters to the Editor, Commentaries and Views, and Articles on science and art. Autophagy is abstracted/indexed in Adis International Ltd (Reactions Weekly), EBSCOhost (Biological Abstracts), Elsevier BV (EMBASE and Scopus), PubMed, Biological Abstracts, Science Citation Index Expanded, Web of Science, and MEDLINE.
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