TY - JOUR
T1 - Calorie Restriction and SIRT3 Trigger Global Reprogramming of the Mitochondrial Protein Acetylome
AU - Hebert, Alexander S.
AU - Dittenhafer-Reed, Kristin E.
AU - Yu, Wei
AU - Bailey, Derek J.
AU - Selen, Ebru Selin
AU - Boersma, Melissa D.
AU - Carson, Joshua J.
AU - Tonelli, Marco
AU - Balloon, Allison J.
AU - Higbee, Alan J.
AU - Westphall, Michael S.
AU - Pagliarini, David J.
AU - Prolla, Tomas A.
AU - Assadi-Porter, Fariba
AU - Roy, Sushmita
AU - Denu, John M.
AU - Coon, Joshua J.
N1 - Funding Information:
This work was funded by NIA grant AG038679 to J.M.D. and T.A.P, NIH grant GM065386 to J.M.D., NIH GM080148 to J.J.C., and Searle Scholars Award and NIH grant RC1DK086410 to D.J.P. K.E.D. was funded by a NSF Graduate Research Fellowship and NIH traineeship (5T32GM08349). We thank A.J. Bureta for figure design.
PY - 2013/1/10
Y1 - 2013/1/10
N2 - Calorie restriction (CR) extends life span in diverse species. Mitochondria play a key role in CR adaptation; however, the molecular details remain elusive. We developed and applied a quantitative mass spectrometry method to probe the liver mitochondrial acetyl-proteome during CR versus control diet in mice that were wild-type or lacked the protein deacetylase SIRT3. Quantification of 3,285 acetylation sites-2,193 from mitochondrial proteins-rendered a comprehensive atlas of the acetyl-proteome and enabled global site-specific, relative acetyl occupancy measurements between all four experimental conditions. Bioinformatic and biochemical analyses provided additional support for the effects of specific acetylation on mitochondrial protein function. Our results (1) reveal widespread reprogramming of mitochondrial protein acetylation in response to CR and SIRT3, (2) identify three biochemically distinct classes of acetylation sites, and (3) provide evidence that SIRT3 is a prominent regulator in CR adaptation by coordinately deacetylating proteins involved in diverse pathways of metabolism and mitochondrial maintenance.
AB - Calorie restriction (CR) extends life span in diverse species. Mitochondria play a key role in CR adaptation; however, the molecular details remain elusive. We developed and applied a quantitative mass spectrometry method to probe the liver mitochondrial acetyl-proteome during CR versus control diet in mice that were wild-type or lacked the protein deacetylase SIRT3. Quantification of 3,285 acetylation sites-2,193 from mitochondrial proteins-rendered a comprehensive atlas of the acetyl-proteome and enabled global site-specific, relative acetyl occupancy measurements between all four experimental conditions. Bioinformatic and biochemical analyses provided additional support for the effects of specific acetylation on mitochondrial protein function. Our results (1) reveal widespread reprogramming of mitochondrial protein acetylation in response to CR and SIRT3, (2) identify three biochemically distinct classes of acetylation sites, and (3) provide evidence that SIRT3 is a prominent regulator in CR adaptation by coordinately deacetylating proteins involved in diverse pathways of metabolism and mitochondrial maintenance.
UR - https://www.scopus.com/pages/publications/84872276165
U2 - 10.1016/j.molcel.2012.10.024
DO - 10.1016/j.molcel.2012.10.024
M3 - Article
C2 - 23201123
AN - SCOPUS:84872276165
SN - 1097-2765
VL - 49
SP - 186
EP - 199
JO - Molecular cell
JF - Molecular cell
IS - 1
ER -