22 March 2024
John Albeck
Department of Molecular and Cell Biology
UC Davis
Cellular energetic status depends on a balance of nutrient catabolism and biosynthesis. In single-celled organisms, homeostasis is largely maintained via feedback between metabolites and enzymes. In multicellular organisms, additional control is orchestrated by a protein regulatory network centered on two kinases: mTOR, which stimulates biosynthetic activity, and AMPK, which favors catabolism. In mammals, these kinases are essential for organismal viability but are dispensable within individual cultured cells. Furthermore, mTOR and AMPK are integrated with growth factor signaling pathways such as RAS/ERK and PI3K/AKT, and they have been implicated repeatedly in longevity and disease. These observations raise questions about the nature of mTOR/AMPK control over cellular metabolism and homeostasis: What are the essential cellular functions that mTOR and AMPK perform to maintain organismal health? On what time scales do they operate? How does a cell under homeostatic control by mTOR/AMPK differ from a cell lacking such control? Recently, insights into these questions have become accessible by combining live-cell fluorescent biosensors for both metabolites and kinase activities. In this theory lunch, I will discuss data obtained from this approach and potential implications for understanding the connections between cellular and organismal metabolic homeostasis.