The AMPK Signalling Pathway Coordinates Cell Growth, Autophagy and Metabolism

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2011 Sep 6

PMID 21892142

Citations 1471

Authors

Maria M Mihaylova

Reuben J Shaw

Affiliations

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Abstract

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.

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References

Dequiedt F, Martin M, von Blume J, Vertommen D, Lecomte E, Mari N . New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases. Mol Cell Biol. 2006; 26(19):7086-102. PMC: 1592903. DOI: 10.1128/MCB.00231-06. View

Zaugg K, Yao Y, Reilly P, Kannan K, Kiarash R, Mason J . Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev. 2011; 25(10):1041-51. PMC: 3093120. DOI: 10.1101/gad.1987211. View

Bokko P, Francione L, Bandala-Sanchez E, Ahmed A, Annesley S, Huang X . Diverse cytopathologies in mitochondrial disease are caused by AMP-activated protein kinase signaling. Mol Biol Cell. 2007; 18(5):1874-86. PMC: 1855013. DOI: 10.1091/mbc.e06-09-0881. View

Zheng B, Cantley L . Regulation of epithelial tight junction assembly and disassembly by AMP-activated protein kinase. Proc Natl Acad Sci U S A. 2007; 104(3):819-22. PMC: 1783397. DOI: 10.1073/pnas.0610157104. View

Amato S, Liu X, Zheng B, Cantley L, Rakic P, Man H . AMP-activated protein kinase regulates neuronal polarization by interfering with PI 3-kinase localization. Science. 2011; 332(6026):247-51. PMC: 3325765. DOI: 10.1126/science.1201678. View

Foretz M, Hebrard S, Leclerc J, Zarrinpashneh E, Soty M, Mithieux G . Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest. 2010; 120(7):2355-69. PMC: 2898585. DOI: 10.1172/JCI40671. View

Baena-Gonzalez E, Rolland F, Thevelein J, Sheen J . A central integrator of transcription networks in plant stress and energy signalling. Nature. 2007; 448(7156):938-42. DOI: 10.1038/nature06069. View

Hedbacker K, Carlson M . SNF1/AMPK pathways in yeast. Front Biosci. 2007; 13:2408-20. PMC: 2685184. DOI: 10.2741/2854. View

Grahame Hardie D . AMP-activated protein kinase as a drug target. Annu Rev Pharmacol Toxicol. 2006; 47:185-210. DOI: 10.1146/annurev.pharmtox.47.120505.105304. View

10.

Inoue E, Yamauchi J . AMP-activated protein kinase regulates PEPCK gene expression by direct phosphorylation of a novel zinc finger transcription factor. Biochem Biophys Res Commun. 2006; 351(4):793-9. DOI: 10.1016/j.bbrc.2006.10.124. View

11.

Bass J, Takahashi J . Circadian integration of metabolism and energetics. Science. 2010; 330(6009):1349-54. PMC: 3756146. DOI: 10.1126/science.1195027. View

12.

Lee J, Park S, Takahashi Y, Wang H . The association of AMPK with ULK1 regulates autophagy. PLoS One. 2010; 5(11):e15394. PMC: 2972217. DOI: 10.1371/journal.pone.0015394. View

13.

Nishimura I, Yang Y, Lu B . PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell. 2004; 116(5):671-82. DOI: 10.1016/s0092-8674(04)00170-9. View

14.

Dentin R, Girard J, Postic C . Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver. Biochimie. 2005; 87(1):81-6. DOI: 10.1016/j.biochi.2004.11.008. View

15.

Drewes G, Ebneth A, Preuss U, Mandelkow E, Mandelkow E . MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. Cell. 1997; 89(2):297-308. DOI: 10.1016/s0092-8674(00)80208-1. View

16.

Shang L, Chen S, Du F, Li S, Zhao L, Wang X . Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc Natl Acad Sci U S A. 2011; 108(12):4788-93. PMC: 3064373. DOI: 10.1073/pnas.1100844108. View

17.

Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y . Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol. 2000; 150(6):1507-13. PMC: 2150712. DOI: 10.1083/jcb.150.6.1507. View

18.

Bungard D, Fuerth B, Zeng P, Faubert B, Maas N, Viollet B . Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation. Science. 2010; 329(5996):1201-5. PMC: 3922052. DOI: 10.1126/science.1191241. View

19.

Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F . Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006; 127(6):1109-22. DOI: 10.1016/j.cell.2006.11.013. View

20.

Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J . Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001; 108(8):1167-74. PMC: 209533. DOI: 10.1172/JCI13505. View