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Figures
- Fig. 1.
Physiological role of AMPK in the cell. Catabolism `charges up the battery' by converting ADP to ATP (bottom curved arrow) whereas ATP-consuming processes convert ATP to ADP (top curved arrow). If a cellular stress causes the rate of catabolism to fail to keep pace with the rate of ATP consumption, ADP levels will rise and ATP levels will fall. ADP is converted into AMP by adenylate kinase and this, combined with the fall in ATP, will activate AMPK. AMPK then promotes the restoration of energy balance by stimulating catabolism and inhibiting ATP-consuming processes.
- Fig. 2.
Conserved domains in AMPK subunits: (A) α subunits, (B) β subunits and (C) γ subunits. The proposed function of each domain is indicated. The two isoforms of the α (α1, α2) and β (β1, β2) subunits have very similar structures, but the three isoforms of the γ subunit (γ1, γ2, γ3) contain variable N-terminal regions of unknown function, and are drawn separately. [Redrawn from Hardie et al. (Hardie et al., 2003).]
- Fig. 3.
Phylogenetic tree of the AMPK-related protein kinases. [Based on Manning et al. (Manning et al., 2002).]
- Table 1.
Stresses that activate AMPK
Type of treatment Treatment Primary reference Respiratory chain inhibitors Antimycin A Witters et al., 1991 Azide Witters et al., 1991 Nitric oxide Almeida et al., 2004 ATP synthase inhibitor Oligomycin Marsin et al., 2000 Mitochondrial uncouplers Dinitrophenol Witters et al., 1991 Over-expression of UCP1 Matejkova et al., 2004 Over-expression of UCP3 Schrauwen et al., 2004 TCA cycle inhibitor Arsenite Corton et al., 1994 Environmental stresses Heat shock Corton et al., 1994 Oxidative stress Choi et al., 2001 Osmotic stress Fryer et al., 2002 Metabolic stresses Ischaemia Kudo et al., 1995 Hypoxia Marsin et al., 2000 Low glucose Salt et al., 1998 Exercise (muscle) Winder and Hardie, 1996 Contraction (muscle) Hutber et al., 1997; Vavvas et al., 1997 Biguanide drugs Metformin Zhou et al., 2001 Phenformin Hawley et al., 2003 Thiazolidinedione drugs Rosiglitazone Fryer et al., 2002 Pioglitazone Saha et al., 2004 - Fig. 4.
Targets for AMPK. Target proteins and processes activated by AMPK activation are shown in green, and those inhibited by AMPK activation are shown in red. Where the effect is caused by a change in gene expression, an upward-pointing green arrow next to the protein indicates an increase, whereas a downward-pointing red arrow indicates a decrease in expression. Abbreviations: ACC1/ACC2, 1 (α) and 2 (β) isoforms of acetyl-CoA carboxylase; CD36/FAT, CD36/fatty acid translocase; CFTR, cystic fibrosis transmembrane regulator; EF2, elongation factor-2; eNOS/nNOS. endothelial/neuronal isoforms of nitric oxide synthase; FAS, fatty acid synthase; G6Pase, glucose-6-phosphatase; GLUT1/4, glucose transporters; GS, glycogen synthase; HMGR, 3-hydroxy-3-methyl-CoA reductase; HSL, hormone-sensitive lipase; MEF2, myocyte-specific enhancer factor-2; NRF1, nuclear respiratory factor-1; PEPCK, phosphoenolpyruvate carboxykinase; PGC1α, peroxisome proliferator-activated receptor-γ co-activator-1α; TOR, mammalian target of rapamycin.
- Fig. 5.
Regulation of protein synthesis and cell growth by AMPK and PKB/Akt by the mTOR pathway. Cellular stresses activate AMPK because the increase in AMP promotes its phosphorylation by LKB1; whereas growth factors activate PKB/Akt because the increase in phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] promotes its phosphorylation by PDK1. AMPK and PKB/Akt phosphorylate TSC2 at different sites, and this stimulates or inhibits, respectively, the ability of the TSC1-TSC2 complex to inhibit TOR. Amino acids also stimulate TOR through the TSC complex. TOR in turn stimulates protein synthesis, and hence cell growth, through ribosomal protein S6 kinase 1 (S6K1) and elongation factor-4E binding protein 1 (4E-BP1). The molecular events immediately upstream and downstream of TOR in this pathway are not shown in detail and remain incompletely understood.
Article navigation
- Top
- Article
- Summary
- Introduction
- Structure of the AMPK complex
- Regulation of the AMPK complex
- Mammalian AMPK is activated by stresses that cause ATP depletion
- Physiological roles of AMPK orthologues in yeast and plants
- Regulation of whole body energy intake and expenditure
- Identification of the upstream kinase, LKB1-STRAD-MO25
- Downstream targets of AMPK
- Conclusions and perspectives
- Acknowledgements
- References
- Figures & tables
- Info & metrics
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