AMPKed up

By Jef Akst AMPKed up © Biophoto Associates / Photo Researchers, Inc. The paper: S. Jäger et al., “AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha,” Proc Natl Acad Sci, 104(29):12017–22, 2007. (Cited in 106 papers) The finding: AMP-activated kinase (AMPK) plays a major role in the regulation of cellular metabolism, increasing gene expression in a va

Jef Akst
Jef Akst

Jef (an unusual nickname for Jennifer) got her master’s degree from Indiana University in April 2009 studying the mating behavior of seahorses. After four years of diving off the Gulf...

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Feb 1, 2010

AMPKed up

© Biophoto Associates / Photo Researchers, Inc.

The paper:
S. Jäger et al., “AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha,” Proc Natl Acad Sci, 104(29):12017–22, 2007. (Cited in 106 papers)

The finding:
AMP-activated kinase (AMPK) plays a major role in the regulation of cellular metabolism, increasing gene expression in a variety of metabolic pathways when a cell is energy-deprived, but how it causes these changes was unclear. One target gene, peroxisome-proliferator-activated receptor Υ coactivator 1α (PGC-1α), is another key player in metabolism. By injecting AMPK activators into mice with and without PGC-1α in their skeletal muscle cells (but carrying PGC-1α in other cell types), cellular biochemist Bruce Spiegelman of Harvard Medical School and his colleagues demonstrated that AMPK directly activates PGC-1α —which in turn mediates AMPK’s effects.

The mechanism:
Using mass spectrometry analysis, Spiegelman and his...

The concern:
To date, there have been no follow-up studies confirming these findings or demonstrating their relevance during normal metabolism and energy depletion, says Thomson. “That’s surprising to me,” he says.

The next step:
Spiegelman’s lab is currently investigating whether this mechanism of PGC-1α activation holds true in other parts of the body. “We have no reason to think it’s specific for muscle,” Spiegelman says.

Genes regulated by AMPK activation of PGC-1α:
GLUT4, PGC-1α, cytochrome c, UCP-1, UCP-3

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