LA JOLLA, CAResearchers at the Salk Institute for Biological Studies have discovered how AMPK, a metabolic master switch that springs into gear when cells run low on energy, revs up a cellular recycling program to free up essential molecular building blocks in times of need.
In a paper published in the Dec. 23, 2010 edition of Science Express, a team led by Reuben Shaw, PhD., Howard Hughes Medical Institute Early Career Scientist and Hearst Endowment assistant professor in the Salk's Molecular and Cell Biology Laboratory, reports that AMPK activates a cellular recycling process known as autophagy by activating an enzyme known as ATG1, that jumpstarts the process.
The newly uncovered direct molecular connection between AMPK and ATG1 is significant because dysfunctions in both AMPK signaling and autophagy are implicated in a plethora of aging-related diseases, including type II diabetes, cancer, and neurodegenerative diseases such Parkinson's and Alzheimers.
Despite its ominous namederived from "self" (auto) and "eating" (phagy)cells use autophagy to dispose of debris before it becomes toxic enough to kill a cell. "Autophagy is an ancient process that evolved to break down components cells don't need to create things they do need," says Dan Egan, a graduate student in Shaw's lab and the study's first author.
Previously, Shaw's lab had not only demonstrated that AMPK is deregulated in certain forms of cancer but also that the enzyme is a critical target of the type 2 diabetes drug metformin. "Taking a drug that activates this pathway, like metformin, is the equivalent of taking several different drugs," says Shaw, reeling off a list of anti-tumor and anti-diabetes pathways activated by AMPK. "Now we can add regulation of autophagy to that list."
Shaw's laboratory has not previously studied autophagy but has had a long-term interest in AMPK, which senses when energy is low and slows cell growth. "Since A
|Contact: Gina Kirchweger|