AMPK in Health and Disease

Abstract

The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) αβγ heterotrimer has emerged as an important integrator of signals that control energy balance through the regulation of multiple biochemical pathways in all eukaryotes. In this review, we begin with the discovery of the AMPK family and discuss the recent structural studies that have revealed the molecular basis for AMP binding to the enzyme's γ subunit. AMPK's regulation involves autoinhibitory features and phosphorylation of both the catalytic α subunit and the β-targeting subunit. We review the role of AMPK at the cellular level through examination of its many substrates and discuss how it controls cellular energy balance. We look at how AMPK integrates stress responses such as exercise as well as nutrient and hormonal signals to control food intake, energy expenditure, and substrate utilization at the whole body level. Lastly, we review the possible role of AMPK in multiple common diseases and the role of the new age of drugs targeting AMPK signaling.

Effect of L-carnitine Supplementation on Nutritional Status and Physical Performance Under Calorie Restriction

“…Both, AMPK activation and fatty acid oxidation are correlated, especially in rodents. Despite this association incongruity exists between them [43]. This might support the trend observed in CPT-1 and AMPK activity in this study.…”

“…AMPK detects shifts in AMP:ATP ratio and therefore when ATP is abundant AMPK has lower activity. Being a metabolic stress sensing protein kinase, it controls the energy balance and increases fatty acid oxidation [43]. It is also a glycogen sensor and may be inhibited by glycogen [44].…”

AMPK activation protects cells from oxidative stress‐induced senescence via autophagic flux restoration and intracellular NAD + elevation

“…The most commonly described mechanism underlying the effects of AMPK on autophagy is suppression of the mTORC1 pathway (Mihaylova & Shaw, 2011; Salminen & Kaarniranta, 2012). Several pharmacological activators of AMPK, such as metformin and berberine, have been characterized, and their potential for the treatment of metabolic, neurodegenerative and other aging‐related diseases is well recognized (Steinberg & Kemp, 2009; Mo et al ., 2014). …”

AMPK β1 reduces tumor progression and improves survival in p53 null mice

“…The AMP‐activated protein kinase (AMPK) is an α, β, γ heterotrimer that senses changes in cellular energy status, and whose activity is reduced under conditions of nutrient surplus such as obesity and diabetes (Ruderman et al ., 2013; Steinberg and Kemp, 2009). AMPK activation by the upstream AMPK kinase LKB1 causes regulation of multiple branches of cellular metabolism that may be important for limiting cancer cell proliferation (Mihaylova and Shaw, 2011).…”