Figure 4.
The SIRT1-AMPK metabolic control network. Conditions of perceived energy deprivation, such as fasting, calorie restriction (CR), and exercise, increase the AMP/ATP ratio and activate AMP-activated protein kinase (AMPK). Energy deprivation also increases nicotinamide adenine dinucleotide (NAD+) levels and activates the NAD+-dependent deacetylase activity of SIRT1. Activated AMPK and SIRT1 converge by activating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) via phosphorylation and deacetylation, respectively, to induce mitochondrial biogenesis and fatty acid oxidation. Cross talk in this pathway occurs because AMPK activity increases NAD+, and SIRT1 also activates AMPK.