PMID- 23688429
OWN - NLM
STAT- MEDLINE
DCOM- 20130820
LR  - 20211021
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 435
IP  - 4
DP  - 2013 Jun 14
TI  - A novel PGC-1alpha isoform in brain localizes to mitochondria and associates with 
      PINK1 and VDAC.
PG  - 671-7
LID - S0006-291X(13)00824-3 [pii]
LID - 10.1016/j.bbrc.2013.05.041 [doi]
AB  - Peroxisome proliferator-activated receptor-gamma co-activator 1alpha (PGC-1alpha) and 
      PTEN-induced putative kinase 1 (PINK1) are powerful regulators of mitochondrial 
      function. Here, we report that a previously unrecognized, novel 35 kDa PGC-1alpha 
      isoform localizes to the mitochondrial inner membrane and matrix in brain as 
      determined by protease protection and carbonate extraction assays, as well as by 
      immunoelectron microscopy. Immunoelectron microscopy and import experiments in 
      vitro revealed that 35 kDa PGC-1alpha colocalizes and interacts with the 
      voltage-dependent anion channel (VDAC), and that its import depends on VDAC. 
      Valinomycin treatment which depolarizes the membrane potential, abolished 
      mitochondrial localization of the 35 kDa PGC-1alpha. Using blue native-PAGE, 
      co-immunoprecipitation, and immunoelectron microscopy analyses, we found that the 
      35 kDa PGC-1alpha binds and colocalizes with PINK1 in brain mitochondria. This is the 
      first report regarding mitochondrial localization of a novel 35 kDa PGC-1alpha 
      isoform and its association with PINK1, suggesting possible regulatory roles for 
      mitochondrial function in the brain.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Choi, Joungil
AU  - Choi J
AD  - Department of Neurology, University of Maryland, Baltimore, MD 21201, USA. 
      jochoi@som.umaryland.edu
FAU - Batchu, Vera Venkatanaresh Kumar
AU  - Batchu VV
FAU - Schubert, Manfred
AU  - Schubert M
FAU - Castellani, Rudolph J
AU  - Castellani RJ
FAU - Russell, James W
AU  - Russell JW
LA  - eng
GR  - P30 DK072488/DK/NIDDK NIH HHS/United States
GR  - R21 RR024888/RR/NCRR NIH HHS/United States
GR  - RR024888/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130517
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Protein Isoforms)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Voltage-Dependent Anion Channels)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (PTEN-induced putative kinase)
SB  - IM
MH  - Animals
MH  - Hippocampus/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/*metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Protein Isoforms/metabolism
MH  - Protein Kinases/*metabolism
MH  - Tissue Distribution
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors
MH  - Voltage-Dependent Anion Channels/*metabolism
PMC - PMC3733220
MID - NIHMS482235
COIS- Competing Interests: The authors declare no conflict of interest.
EDAT- 2013/05/22 06:00
MHDA- 2013/08/21 06:00
PMCR- 2014/06/14
CRDT- 2013/05/22 06:00
PHST- 2013/05/01 00:00 [received]
PHST- 2013/05/02 00:00 [accepted]
PHST- 2013/05/22 06:00 [entrez]
PHST- 2013/05/22 06:00 [pubmed]
PHST- 2013/08/21 06:00 [medline]
PHST- 2014/06/14 00:00 [pmc-release]
AID - S0006-291X(13)00824-3 [pii]
AID - 10.1016/j.bbrc.2013.05.041 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2013 Jun 14;435(4):671-7. doi: 
      10.1016/j.bbrc.2013.05.041. Epub 2013 May 17.