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Cell Rep. 2015 Apr 28;11(4):657-70. doi: 10.1016/j.celrep.2015.03.057. Epub 2015 Apr 16.

Compartmentalized AMPK signaling illuminated by genetically encoded molecular sensors and actuators.

Author information

1
Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Center for Cell Dynamics, Institute for Basic Biomedical Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: takmi565@gmail.com.
2
Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Center for Cell Dynamics, Institute for Basic Biomedical Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
3
Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Center for Cell Dynamics, Institute for Basic Biomedical Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
4
Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
5
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
6
Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Center for Cell Dynamics, Institute for Basic Biomedical Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: jzhang32@jhmi.edu.
7
Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Center for Cell Dynamics, Institute for Basic Biomedical Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Precursory Research for Embryonic Science and Technology (PRESTO) Investigator, Japan Science and Technology Agency (JST), Saitama 332-0012, Japan. Electronic address: jctinoue@jhmi.edu.

Abstract

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 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.

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PMID:
25892241
PMCID:
PMC4417068
DOI:
10.1016/j.celrep.2015.03.057
[Indexed for MEDLINE]
Free PMC Article

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