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Title: A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC

Abstract

Highlights: •Novel 35 kDa PGC-1α localizes to mitochondrial inner membrane and matrix in brain. •Mitochondrial localization of 35 kDa PGC-1α depends on VDAC protein. •Mitochondrial localization of 35 kDa PGC-1α depends on membrane potential. •The 35 kDa PGC-1α associates and colocalizes with PINK in brain mitochondria. -- Abstract: Peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) and PTEN-induced putative kinase 1 (PINK1) are powerful regulators of mitochondrial function. Here, we report that a previously unrecognized, novel 35 kDa PGC-1α 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-1α 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-1α. Using blue native-PAGE, co-immunoprecipitation, and immunoelectron microscopy analyses, we found that the 35 kDa PGC-1α binds and colocalizes with PINK1 in brain mitochondria. This is the first report regarding mitochondrial localization of a novel 35 kDa PGC-1α isoform and its association with PINK1, suggesting possible regulatory roles for mitochondrial function in the brain.

Authors:
 [1];  [1];  [2];  [3];  [1]
  1. Department of Neurology, University of Maryland, Baltimore, MD 21201 (United States)
  2. National Institute of Neurological Disorders and Stroke, Baltimore, MD 21201 (United States)
  3. Department of Pathology, University of Maryland, Baltimore, MD 21201 (United States)
Publication Date:
OSTI Identifier:
22239630
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 435; Journal Issue: 4; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIONS; BRAIN; CARBONATES; ELECTRIC POTENTIAL; EXTRACTION; IN VITRO; MITOCHONDRIA; RECEPTORS; VALINOMYCIN

Citation Formats

Choi, Joungil, Veterans Affairs Medical Center, Baltimore, MD 21201, Batchu, Vera Venkatanaresh Kumar, Veterans Affairs Medical Center, Baltimore, MD 21201, Schubert, Manfred, Castellani, Rudolph J., Russell, James W., and Veterans Affairs Medical Center, Baltimore, MD 21201. A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.05.041.
Choi, Joungil, Veterans Affairs Medical Center, Baltimore, MD 21201, Batchu, Vera Venkatanaresh Kumar, Veterans Affairs Medical Center, Baltimore, MD 21201, Schubert, Manfred, Castellani, Rudolph J., Russell, James W., & Veterans Affairs Medical Center, Baltimore, MD 21201. A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC. United States. https://doi.org/10.1016/J.BBRC.2013.05.041
Choi, Joungil, Veterans Affairs Medical Center, Baltimore, MD 21201, Batchu, Vera Venkatanaresh Kumar, Veterans Affairs Medical Center, Baltimore, MD 21201, Schubert, Manfred, Castellani, Rudolph J., Russell, James W., and Veterans Affairs Medical Center, Baltimore, MD 21201. 2013. "A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC". United States. https://doi.org/10.1016/J.BBRC.2013.05.041.
@article{osti_22239630,
title = {A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC},
author = {Choi, Joungil and Veterans Affairs Medical Center, Baltimore, MD 21201 and Batchu, Vera Venkatanaresh Kumar and Veterans Affairs Medical Center, Baltimore, MD 21201 and Schubert, Manfred and Castellani, Rudolph J. and Russell, James W. and Veterans Affairs Medical Center, Baltimore, MD 21201},
abstractNote = {Highlights: •Novel 35 kDa PGC-1α localizes to mitochondrial inner membrane and matrix in brain. •Mitochondrial localization of 35 kDa PGC-1α depends on VDAC protein. •Mitochondrial localization of 35 kDa PGC-1α depends on membrane potential. •The 35 kDa PGC-1α associates and colocalizes with PINK in brain mitochondria. -- Abstract: Peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) and PTEN-induced putative kinase 1 (PINK1) are powerful regulators of mitochondrial function. Here, we report that a previously unrecognized, novel 35 kDa PGC-1α 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-1α 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-1α. Using blue native-PAGE, co-immunoprecipitation, and immunoelectron microscopy analyses, we found that the 35 kDa PGC-1α binds and colocalizes with PINK1 in brain mitochondria. This is the first report regarding mitochondrial localization of a novel 35 kDa PGC-1α isoform and its association with PINK1, suggesting possible regulatory roles for mitochondrial function in the brain.},
doi = {10.1016/J.BBRC.2013.05.041},
url = {https://www.osti.gov/biblio/22239630}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 435,
place = {United States},
year = {Fri Jun 14 00:00:00 EDT 2013},
month = {Fri Jun 14 00:00:00 EDT 2013}
}