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SIRT5 regulation has dramatic effect on mitochondrial metabolism
Date:12/11/2013

The Sirtuin family of protein deacylases has received considerable attention in recent years due to its links to longevity, diabetes, cancer, and metabolic regulation. In a new study published in the Dec. 3rd 2013 issue of Cell Metabolism, Buck Institute researchers have now identified widespread regulation of proteins involved in metabolism by the mitochondrial sirtuin, SIRT5. Using a novel quantitative proteomic method developed at the Buck Institute, the Gibson lab in collaboration with Eric Verdin's group at the Gladstone Institute was able to identify hundreds of proteins in the mitochondria that undergo modification by lysine succinylation and its subsequent regulation by SIRT5. These findings have widespread implications for understanding metabolic function in both normal and disease states.

"Before you can study a process you first have to understand who the players are," says Bradford Gibson, PhD, Professor and Director of Chemistry and Mass Spectrometry at the Buck Institute. SIRT5 is found within mitochondria, a cellular organelle primarily responsible for energy production and homeostasis, which is present in virtually all cells in our body. By quantifying the differences between mice lacking the SIRT5 gene and control animals, Gibson and his colleagues discovered that SIRT5 selectively removes specific sites of succinyl modifications in over 140 different proteins that are involved in essential metabolic pathways, including fatty acid-oxidation, oxidative phosphorylation, and ketone body production. Matthew Rardin, a postdoctoral fellow in the Gibson's lab and a lead author of the study explains, "Within mitochondria there is widespread succinylation across multiple proteins and pathways, and SIRT5 appears to be the only enzyme within mitochondria that is responsible for the regulation of this structural modification."

"We have found that lysine succinylation can have huge effects on enzyme activity," adds Gibson. Succi
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Contact: Kris Rebillot
krebillot@buckinstitute.org
415-209-2080
Buck Institute for Age Research
Source:Eurekalert

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