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How cells running on empty trigger fuel recycling
Date:12/23/2010

MPK plays such a central role in regulating our cells' energy household, we wanted to know how it exerts its power over so many cellular processes," says Shaw.

His team initiated the study by defining a unique targeting sequence used by AMPK to transmit its signals and then using bioinformatics and biochemistry to identify proteins that act as AMPK targets. One of the prime suspects identified in that that effort was the protein Atg1/ULK1, a factor that triggers autophagy in yeast.

To test the effects on autophagy of deregulating these enzymes, the group focused on large intracellular structures called mitochondria, whose role is to generate energy. "Mitochondria are easily damaged in detoxifying tissues like liver," explains Shaw. "A critical way that defective mitochondria are turned over is through a special form of autophagy called mitophagy."

In that case, cells would envelope their unhealthy mitochondria in a membrane, dump them in a cellular acid pit, and recycle the remains. If AMPK initiated the process, cells genetically engineered to lack AMPK might show altered mitochondrial turnover compared to normal cells.

And that is precisely what the researchers saw: liver cells in which AMPK had been eliminated contained too many mitochondria, many of which looked spindly, indicating they were moribund, and confirming that AMPK was directing autophagic waste disposal. "We found that the ability to recycle their defective mitochondria allowed cells to survive starvation better," says Shaw.

To tie it all together, the researchers used the roundworm C. elegans, a popular model system in aging research, to show that activated AMPK directly activated autophagy through a signal relayed by the worm version of Atg1/ULK1experiments done in collaboration with Malene Hansen, Ph.D., of La Jolla's Sanford-Burnham Medical Research Institute and with help from Andy Dillin, Ph.D., of Salk's Molecular and Cell Biology Laboratory,'/>"/>

Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-4100 x1340
Salk Institute
Source:Eurekalert  

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