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AMPK: a key regulator of energy stress and calcium-induced autophagy

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Abstract

Autophagy is a well-known cell-survival strategy orchestrated by a conserved set of proteins. It equips the cells with mechanisms to attain homeostasis during unfavorable conditions such as stress by breaking down the cellular components and reusing them for energy as well as for building new components required for survival. A basal level of autophagy is required for achieving homeostasis under normal conditions through regular turnover of macromolecules and organelles. Initiation of autophagy is regulated by two key components of the nutrient/energy sensor pathways; mammalian target of rapamycin 1 (mTORC1) and AMP-activated kinase (AMPK). Under energy-deprived conditions, AMPK is activated triggering autophagy, whereas, in nutrient-rich conditions, the growth-promoting kinase mTORC1 is activated inhibiting autophagy. Thus, the reciprocal regulation of autophagy by AMPK and mTORC1 defines a fundamental mechanism by which cells respond to nutrient availability. Interestingly, cytoplasmic calcium is also found to be an activator of AMPK and autophagy through a calmodulin/CaMKKβ pathway. However, the physiological significance of the regulation of autophagy by cytoplasmic calcium is currently unclear. This review focuses on the current understanding of the mechanism of autophagy and its regulation by AMPK.

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Acknowledgements

We thank Lizanne Oliveira for her critical reading and editing of the manuscript.

Funding

The study in the laboratory is supported by funding from the Department of Biotechnology, Department of Science and Technology, Government of India, (BT/PR27451/BRB/10/1655/2018 and BT/PR32331/BRB/10/1774/2019), and intramural funding from National Centre for Cell Science. The financial support from the Department of Biotechnology, Ministry of Science and Technology, Government of India, to RS, was through a research fellowship.

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    Rimpi Saikia & Jomon Joseph

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Saikia, R., Joseph, J. AMPK: a key regulator of energy stress and calcium-induced autophagy. J Mol Med 99, 1539–1551 (2021). https://doi.org/10.1007/s00109-021-02125-8

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