Compartmentalized AMPK Signaling Illuminated by Genetically Encoded Molecular Sensors and Actuators

Takafumi Miyamoto, Elmer Rho, Vedangi Sample, Hiroki Akano, Masaki Magari, Tasuku Ueno, Kirill Gorshkov, Melinda Chen, Hiroshi Tokumitsu, Jin Zhang, Takanari Inoue

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28 Citations (Scopus)

Abstract

AMP-activated protein kinase (AMPK), whose activity is a critical determinant of cell health, serves afundamental 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, notAMPKα2, 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.

Original languageEnglish
Pages (from-to)657-670
Number of pages14
JournalCell Reports
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 28 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Miyamoto, T., Rho, E., Sample, V., Akano, H., Magari, M., Ueno, T., Gorshkov, K., Chen, M., Tokumitsu, H., Zhang, J., & Inoue, T. (2015). Compartmentalized AMPK Signaling Illuminated by Genetically Encoded Molecular Sensors and Actuators. Cell Reports, 11(4), 657-670. https://doi.org/10.1016/j.celrep.2015.03.057