A cellular energy sensor

One of the central regulators of cellular and organismal metabolism in eukaryotes is AMP-activated protein kinase (AMPK). It is a highly conserved metabolism master regulator, which restores energy balance during metabolic stress both at the cellular and physiological levels. AMPK monitors the ratio of AMP/ATP, and also ADP/ATP, within cells. AMPK is switched on by increases in the AMP/ATP ratio via three mechanisms, all of which are antagonized by decreases in the AMP/ATP ratio: (a) promotion of phosphorylation of Thr172 by upstream activating kinases; (b) inhibition of dephosphorylation of Thr172 by phosphatases; and (c) allosteric activation of the phosphorylated kinase (1). AMPK is distributed in most organs including the liver, heart, and hypothalamus, and even in adipose cells. In addition, AMPK activation in the hypothalamus stimulates appetite in low energy states (2).

AMPK has recently been associated with cellular processes such as autophagy and cell polarity (3). AMPK has also been implicated in several species as a critical modulator of aging through its interactions with mTOR or sirtuins. The kinase is activated in response to stresses that deplete cellular ATP supplies such as low glucose, hypoxia, ischemia, and heat shock. In mammals, there are two genes encoding the AMPK α catalytic subunit (α1 and α2), two β genes (β1 and β2), and three γ subunit genes (γ1, γ2, and γ3) (4).

Due to its role as a central regulator of both lipid and glucose metabolism, AMPK is a potential therapeutic target for the treatment of type II diabetes mellitus, obesity, and cancer (5 and 6).

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  1. AMPK: a cellular energy sensor primarily regulated by AMP.
  2. AMPK as a cellular energy sensor and its function in the organism
  3. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
  4.  AMPK activators: mechanisms of action and physiological activities
  5.  AMPK: an emerging drug target for diabetes and the metabolic syndrome.
  6. Targeting AMPK for cancer prevention and treatment