کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2041387 | 1073158 | 2015 | 14 صفحه PDF | دانلود رایگان |
• Molecular sensors measure AMPK activity at different subcellular locations
• Molecular actuators allow for rapid induction of AMPK inhibition in living cells
• Genetically encoded molecular probes reveal the compartmentalized AMPK regulation
SummaryAMP-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 AMPKα1, not AMPKα2, 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.
Graphical AbstractFigure optionsDownload as PowerPoint slide
Journal: - Volume 11, Issue 4, 28 April 2015, Pages 657–670