Spatial control of AMPK signaling at subcellular compartments

Abstract

AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis that functions to restore the energy balance by phosphorylating its substrates during altered metabolic conditions. AMPK activity is tightly controlled by diverse regulators including its upstream kinases LKB1 and CaMKK2. Recent studies have also identified the localization of AMPK at different intracellular compartments as another key mechanism for regulating AMPK signaling in response to specific stimuli. This review discusses the AMPK signaling associated with different subcellular compartments, including lysosomes, endoplasmic reticulum, mitochondria, Golgi apparatus, nucleus, and cell junctions. Because altered AMPK signaling is associated with various pathologic conditions including cancer, targeting AMPK signaling in different subcellular compartments may present attractive therapeutic approaches for treatment of disease.

Keywords:

• AMPK
• LKB1
• CaMKK2
• lysosome
• endoplasmic reticulum
• mitochondria
• nucleus
• cell junction

Acknowledgements

We apologize to the many colleagues whose related work cannot be cited due to space limitations. We thank Christine Wogan of the Division of Radiation Oncology at The University of Texas MD Anderson Cancer Center for manuscript editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

B. Gan is supported by the Andrew Sabin Family Fellow Award and bridge fund from The University of Texas MD Anderson Cancer Center and National Institutes of Health grant R01CA181196.