PMID- 18031569
OWN - NLM
STAT- MEDLINE
DCOM- 20080225
LR  - 20211020
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 7
IP  - 1
DP  - 2008 Jan
TI  - Dynamic regulation of PGC-1alpha localization and turnover implicates 
      mitochondrial adaptation in calorie restriction and the stress response.
PG  - 101-11
AB  - There is increasing evidence that longevity and stress resistance are connected, 
      but the mechanism is unclear. We report that mitochondria are regulated in 
      response to oxidative stress and calorie restriction through a shared mechanism 
      involving peroxisome proliferator-activated receptor-gamma co-activator 1alpha 
      (PGC-1alpha). We demonstrate that PGC-1alpha subcellular distribution is 
      regulated, and its transcriptional activity is promoted through SIRT1-dependent 
      nuclear accumulation. In addition, the duration of PGC-1alpha activity is 
      regulated by glycogen synthase kinase beta (GSK3beta), which targets PGC-1alpha 
      for intranuclear proteasomal degradation. This mechanism of regulation permits 
      the rapidity and persistence of PGC-1alpha activation to be independently 
      controlled. We provide evidence that this pathway of PGC-1alpha regulation occurs 
      in vivo in mice, both in the oxidative stress response and with calorie 
      restriction. Our data show how mitochondrial function may be adapted in response 
      to external stimuli, and support the concept that such adaptation is critically 
      involved in cellular survival and in lifespan extension by calorie restriction.
FAU - Anderson, Rozalyn M
AU  - Anderson RM
AD  - University of Wisconsin Madison, GRECC VA Hospital, 2500 Overlook Terrace, 
      Madison, WI 53705, USA. rmanderson5@wisc.edu
FAU - Barger, Jamie L
AU  - Barger JL
FAU - Edwards, Michael G
AU  - Edwards MG
FAU - Braun, Kristina H
AU  - Braun KH
FAU - O'Connor, Clare E
AU  - O'Connor CE
FAU - Prolla, Tomas A
AU  - Prolla TA
FAU - Weindruch, Richard
AU  - Weindruch R
LA  - eng
GR  - T32 AG000214/AG/NIA NIH HHS/United States
GR  - P01 AG11915/AG/NIA NIH HHS/United States
GR  - T32 AG000213/AG/NIA NIH HHS/United States
GR  - P01 AG011915/AG/NIA NIH HHS/United States
GR  - P20 CA103697/CA/NCI NIH HHS/United States
GR  - T32 AG00214/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20071121
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Animals
MH  - *Caloric Restriction
MH  - Gene Expression Regulation
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - In Vitro Techniques
MH  - Membrane Potential, Mitochondrial
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Mitochondria/chemistry/*metabolism
MH  - NIH 3T3 Cells
MH  - Oxidative Stress
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Sirtuin 1
MH  - Sirtuins/metabolism
MH  - Trans-Activators/analysis/*genetics/*metabolism
MH  - Transcription Factors
PMC - PMC2253697
EDAT- 2007/11/23 09:00
MHDA- 2008/02/26 09:00
PMCR- 2008/02/25
CRDT- 2007/11/23 09:00
PHST- 2007/11/23 09:00 [pubmed]
PHST- 2008/02/26 09:00 [medline]
PHST- 2007/11/23 09:00 [entrez]
PHST- 2008/02/25 00:00 [pmc-release]
AID - ACE357 [pii]
AID - 10.1111/j.1474-9726.2007.00357.x [doi]
PST - ppublish
SO  - Aging Cell. 2008 Jan;7(1):101-11. doi: 10.1111/j.1474-9726.2007.00357.x. Epub 
      2007 Nov 21.