Apr, 2015
Compartmentalized AMPK Signaling Illuminated by Genetically Encoded Molecular Sensors and Actuators
Cell Reports
- Volume
- 11
- Number
- 4
- First page
- 657
- Last page
- 670
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.celrep.2015.03.057
- Publisher
- CELL PRESS
AMP-activated protein kinase (AMPK), whose activity is a critical determinant of cell health, serves a fundamental role in integrating extracellular and intracellular nutrient information into signals that regulate various metabolic processes. Despite the importance of AMPK, its specific roles within the different intracellular spaces remain unresolved, largely due to the lack of real-time, organelle-specific AMPK activity probes. Here, we present a series of molecular tools that allows for the measurement of AMPK activity at the different subcellular localizations and that allows for the rapid induction of AMPK inhibition. We discovered that AMPK alpha 1, not AMPK alpha 2, was the subunit that preferentially conferred spatial specificity to AMPK, and that inhibition of AMPK activity at the mitochondria was sufficient for triggering cytosolic ATP increase. These findings suggest that genetically encoded molecular probes represent a powerful approach for revealing the basic principles of the spatiotemporal nature of AMPK regulation.
- Link information
- ID information
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- DOI : 10.1016/j.celrep.2015.03.057
- ISSN : 2211-1247
- Pubmed ID : 25892241
- Web of Science ID : WOS:000353902600014