Related Experiment Video
Updated: Jun 21, 2025
08:04
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
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New developments in AMPK and mTORC1 cross-talk
William J Smiles1,2, Ashley J Ovens3, Bruce E Kemp4,5,6
1Metabolic Signalling Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
Essays in Biochemistry
|July 12, 2024
Summary
Cellular energy balance relies on AMPK and mTORC1 kinases. These proteins interact to control cell growth, survival, and autophagy, with new findings highlighting their isoform-specific roles in cancer.
Area of Science:
- Cellular Biology
- Metabolism
- Biochemistry
Background:
- Metabolic homeostasis is crucial for cell growth and proliferation, maintained by nutrient-sensing kinases AMPK and mTORC1.
- AMPK promotes catabolism, while mTORC1 promotes anabolism, acting as counteracting regulators of cellular energy.
- These kinases control cell survival, growth, and proliferation by sensing nutrient availability.
Purpose of the Study:
- To provide a comprehensive overview of the cross-talk between AMPK and mTORC1.
- To discuss the mechanisms of AMPK/mTORC1 activation at the lysosome.
- To highlight recent findings on mTORC1 feedback to AMPK isoforms and their relevance in cancer.
Main Methods:
- Literature review of discoveries from the early 2000s to recent reports.
- Analysis of direct and indirect phosphorylation events regulating AMPK, mTORC1, and ULK1.
- Examination of lysosomal activation mechanisms for AMPK and mTORC1.
Main Results:
- AMPK and mTORC1 cross-talk through phosphorylation to regulate each other's activity and ULK1, the autophagy initiator.
- Divergent mechanisms of AMPK/mTORC1 cross-talk and lysosomal activation pathways have been identified.
- mTORC1 feedback extends to specific AMPK isoforms, relevant to cancer pathogenesis.
Conclusions:
- The intricate cross-talk between AMPK and mTORC1 is vital for cellular adaptation to energy and nutritional states.
- Lysosomes play a key role in the activation of these critical metabolic regulators.
- Understanding isoform-specific AMPK regulation by mTORC1 offers new insights into cancer biology and potential therapeutic targets.
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