Spatial Regulation of AMPK Signaling Revealed by a Sensitive Kinase Activity Reporter

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jul 5

PMID 35790710

Authors

Danielle L Schmitt

Stephanie D Curtis

Anne C Lyons

Jin-Fan Zhang

Mingyuan Chen

Catherine Y He

Sohum Mehta

Reuben J Shaw

Jin Zhang

Affiliations

Soon will be listed here.

Abstract

AMP-activated protein kinase (AMPK) is a master regulator of cellular energetics which coordinates metabolism by phosphorylating a plethora of substrates throughout the cell. But how AMPK activity is regulated at different subcellular locations for precise spatiotemporal control over metabolism is unclear. Here we present a sensitive, single-fluorophore AMPK activity reporter (ExRai AMPKAR), which reveals distinct kinetic profiles of AMPK activity at the mitochondria, lysosome, and cytoplasm. Genetic deletion of the canonical upstream kinase liver kinase B1 (LKB1) results in slower AMPK activity at lysosomes but does not affect the response amplitude at lysosomes or mitochondria, in sharp contrast to the necessity of LKB1 for maximal cytoplasmic AMPK activity. We further identify a mechanism for AMPK activity in the nucleus, which results from cytoplasmic to nuclear shuttling of AMPK. Thus, ExRai AMPKAR enables illumination of the complex subcellular regulation of AMPK signaling.

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