A paradigm shift: AMPK negatively regulates ULK1 activity.
A paradigm shift: AMPK negatively regulates ULK1 activity.
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范式转变：AMPK 负向调节 ULK1 活性。
DOI：
10.1080/15548627.2023.2223465
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发表时间：
2024
期刊：
影响因子：
13.3
通讯作者：
Kim,Do-Hyung
中科院分区：
文献类型：
--
作者：
Park,Ji-Man;Kim,Do-Hyung
在葡萄糖饥饿的细胞中，巨自噬（下文称为自噬）被认为是有助于细胞存活的能量产生过程。AMPK（腺苷一磷酸活化蛋白激酶）是主要的细胞能量传感器，在葡萄糖饥饿期间被激活。根据该领域目前的范式，AMPK通过结合和磷酸化ULK 1（β-51样激酶1）（负责自噬起始的蛋白激酶）来促进自噬，以响应能量剥夺。然而，据报有相互矛盾的调查结果，使人们对目前建立的模式产生怀疑。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。与目前的范式相反，我们的研究表明AMPK作为ULK 1活性的负调节剂发挥作用。该研究阐明了潜在的机制，并证明了在能量耗尽期间控制自噬和维持细胞弹性的负面作用的重要性。缩写：AMPK：腺苷一磷酸活化蛋白激酶; ULK 1：β-51样激酶1; MTORC 1：雷帕霉素复合物1的机制靶点; ATG 14：自噬相关蛋白14; PIK 3C 3：磷脂酰肌醇3-激酶催化亚基3型;可承诺量：三磷酸腺苷; VPS34：空泡蛋白分选34; BECN 1：Beclin 1; AMPKα：AMPK催化亚基α; LKB 1：肝激酶B1; PIK 3R 4：磷脂酰肌醇3-激酶调节亚基4。
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.