New developments in AMPK and mTORC1 cross-talk

William J. Smiles, Ashley J. Ovens, Bruce E. Kemp, Sandra Galic, Janni Petersen, Jonathan S. Oakhill

Research output: Contribution to journalReview articlepeer-review

76 Downloads (Pure)

Abstract

Metabolic homeostasis and the ability to link energy supply to demand are essential requirements for all living cells to grow and proliferate. Key to metabolic homeostasis in all eukaryotes are AMPK and mTORC1, two kinases that sense nutrient levels and function as counteracting regulators of catabolism (AMPK) and anabolism (mTORC1) to control cell survival, growth and proliferation. Discoveries beginning in the early 2000s revealed that AMPK and mTORC1 communicate, or cross-talk, through direct and indirect phosphorylation events to regulate the activities of each other and their shared protein substrate ULK1, the master initiator of autophagy, thereby allowing cellular metabolism to rapidly adapt to energy and nutritional state. More recent reports describe divergent mechanisms of AMPK/mTORC1 cross-talk and the elaborate means by which AMPK and mTORC1 are activated at the lysosome. Here, we provide a comprehensive overview of current understanding in this exciting area and comment on new evidence showing mTORC1 feedback extends to the level of the AMPK isoform, which is particularly pertinent for some cancers where specific AMPK isoforms are implicated in disease pathogenesis.
Original languageEnglish
Article numberEBC20240007
Number of pages16
JournalEssays in Biochemistry
Early online date12 Jul 2024
DOIs
Publication statusE-pub ahead of print - 12 Jul 2024

Keywords

  • AMPK
  • cancer
  • mechanistic target of rapamycin
  • metabolism
  • signalling

Fingerprint

Dive into the research topics of 'New developments in AMPK and mTORC1 cross-talk'. Together they form a unique fingerprint.

Cite this