[Frontiers in Bioscience 19, 447-474, January 1, 2014]

AMPK: A cellular metabolic and redox sensor. A minireview

Najeeb A Shirwany1, Ming-Hui Zou1

1Section of Molecular Medicine, Department of Medicine, and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

TABLE OF CONTENTS

1. Abstract
2. Sensors in biology
3. Discovery
4. Physiological aspects of AMPK signaling
4.1. AMPK subunits
4.2. AMPK activation
4.3. Upstream AMPK kinases
4.4. Downstream targets of AMPK
5. Metabolic effects of AMPK activation
6. AMPK and mitochondrial biogenesis
7. Role of AMPK in cellular synthetic function
8. Role of AMPK in cell growth and cell death
9. Role of AMPK in membrane excitability and electrochemical gradients
10. Integrative physiological impact of AMPK
11. Role of AMPK in human diseases
11.1. Obesity
11.2. Aging
11.3. Malignant disease
11.4. Neurodegeneration
11.5. Diabetes
12. AMPK and oxidative stress
12.1. Cardiac disease
12.2. Vascular endothelial function
12.3 .Vascular smooth muscle dysfunction
13. Summary and conclusions
14. Acknowledgements
15. Referneces

1. ABSTRACT

AMPK is a serine/threonine kinase that is found in all eukaryotes and is ubiquitously expressed in all organ systems. Once activated, AMPK stimulates hepatic fatty acid oxidation and ketogenesis, inhibits cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibits adipocyte lipolysis and lipogenesis, stimulates skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulates insulin secretion by the pancreas. Thus its importance in many critical cellular processes is well established. For cells it is critical that energy supply and demand are closely matched. AMPK is recognized as a critical integrator of this balance. It is known to be allosterically activated by an increased AMP:ATP ratio. Activation of the kinase switches on catabolic pathways while switching off anabolic ones. It also acts as a redox sensor in endothelial cells where oxidative stress can disturb NO signaling. Abnormal NO signaling leads to disturbed vasodilatory responses. By inhibiting the formation of reactive oxygen species in the endothelium, AMPK can optimize the redox balance in the vasculature. Here, we review the role of AMPK in the cell.