The AMP-activated protein kinase (AMPK) signaling pathway coordinates cell growth, autophagy, & metabolism

By Maria M. Mihaylova, R. Shaw. Nature Cell Biology, 2011

2,755 citations recorded by the source corpus.

One of the central regulators of cellular and organismal metabolism in eukaryotes is AMP-activated protein kinase (AMPK), which is activated when intracellular ATP production decreases. AMPK has critical roles in regulating growth and reprogramming metabolism, and has recently been connected to cellular processes such as autophagy and cell polarity. Here we review a number of recent breakthroughs in the mechanistic understanding of AMPK function, focusing on a number of newly identified downstream effectors of AMPK.

Subfields: Epidemiology, Molecular Biology, Surgery

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Citations in the corpus

• Mitochondria: In Sickness and in Health (2012, background): “AMPK is activated by an increase in AMP:ATP ratio and increased ADP concentrations, both of which accompany a decrease in caloric intake or an increase in energy expenditure (Hardie et al., 2011; Mihaylova and Shaw, 2011).”
• The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression (2019, background): “…was never anticipated by Warburg, his supporters and contemporaries (e.g. DeBerardinis et al. 2008; Vander Heiden et al. 2009; Cairns et al. 2011; Mihaylova and Shaw 2011; Ward and Thompson 2012; Amoedo et al. 2013; Soga 2013; Phan et al. 2014; Liberty and Locasale 2016; Bose and Le 2018; Kato…”
• Ageing as a risk factor for disease. (2012, background): “ATP levels modulate AMPK, which can promote autophagy and also interacts both with the IIS and TOR pathways.”
• Autophagy and Tumor Metabolism (2017, background): “While most tissues have low levels of basal autophagy, it is significantly stimulated by the stressed state – the most well studied is starvation and this is tightly regulated by the mTOR and AMP kinase pathways (Kim and Guan, 2015; Mihaylova and Shaw, 2011; Neufeld, 2010).”
• Mechanisms of Autophagy Initiation (2017, background): “AMPK (AMP-activated protein kinase) upregulates autophagy in response to energy depletion as detected by an increase in cytosolic AMP (54).”
• The role of estrogens in control of energy balance and glucose homeostasis. (2013, background): “It should be noted that AMPK is considered a central regulator of many cellular processes, including cell growth, mitochondrial biogenesis, and oxidative metabolism (262, 263).”
• AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1 (2013, background): “A low energy state results in the activation of AMPK, which, in turn, phosphorylates a host of key cellular proteins to suppress ATP consumption and increase ATP production to restore energy homeostasis (Mihaylova and Shaw, 2011; Viollet et al., 2009).”
• PIP4kγ is a substrate for mTORC1 that maintains basal mTORC1 signaling during starvation (2014, background): “PIP4kg’s role in activating mTORC1 in nutrient-deprived cells seems contrary to the role of LKB1 (liver kinase B1), a tumor suppressor kinase that inhibits mTORC1 activity through phosphorylation of AMPK [AMP (adenosine 5′-monophosphate)–dependent kinase] when ATP concentrations are low (38).”
• NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases (2015, background): “…LRR, leucine-rich-repeat olymorphonuclear leukocytes; POP, PYD-only proteins; PRRs, pattern-recognition MCs, smooth muscle cells; TLRs, toll-like receptors; TNF, tumor necrosis factor; Trx, unfolded protein response eing Biology (B2A), UMR-8256/INSERM ERL-1164, Université Pierre et Marie Curie,”
• Cancer Cell Metabolism: One Hallmark, Many Faces (2012, background): “Upon activation, AMPK stimulates metabolic alterations to limit energy consumption (or enhance energy production) and thus allow for adaptation to a given metabolic stress (44).”