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

Joungil Choi; Vera Venkatanaresh Kumar Batchu; Manfred Schubert; Rudolph J. Castellani; James W. Russell

doi:10.1016/j.bbrc.2013.05.041

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

Joungil Choi^*, Vera Venkatanaresh Kumar Batchu, Manfred Schubert, Rudolph J. Castellani, James W. Russell

^*Corresponding author for this work

Pathology

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19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	671-677
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	435
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2013.05.041
State	Published - Jun 14 2013

Funding

We thank Dr. Daniel Kelly and Ms. Theresa Leone for providing the PGC-1α antibody. This work was supported by Department of Veterans Affairs Biomedical Research Service, Office of Research and Development, Biomedical Laboratory Research and Development ( NEUC-00508S – JWR ), NIH RR024888 (JWR) , VA Baltimore Research and Education Foundation (JC), The Mid-Atlantic Nutrition Obesity Research Center ( NIH P30 DK072488 ), Veterans Administration Research and Development REAP award (JWR, JC), JDRF, and ADA.

Keywords

Brain
Mitochondria
PGC-1α
PINK1
VDAC

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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title = "A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC",

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.",

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author = "Joungil Choi and Batchu, {Vera Venkatanaresh Kumar} and Manfred Schubert and Castellani, {Rudolph J.} and Russell, {James W.}",

note = "Funding Information: We thank Dr. Daniel Kelly and Ms. Theresa Leone for providing the PGC-1α antibody. This work was supported by Department of Veterans Affairs Biomedical Research Service, Office of Research and Development, Biomedical Laboratory Research and Development ( NEUC-00508S – JWR ), NIH RR024888 (JWR) , VA Baltimore Research and Education Foundation (JC), The Mid-Atlantic Nutrition Obesity Research Center ( NIH P30 DK072488 ), Veterans Administration Research and Development REAP award (JWR, JC), JDRF, and ADA.",

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AU - Batchu, Vera Venkatanaresh Kumar

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AU - Castellani, Rudolph J.

AU - Russell, James W.

N1 - Funding Information: We thank Dr. Daniel Kelly and Ms. Theresa Leone for providing the PGC-1α antibody. This work was supported by Department of Veterans Affairs Biomedical Research Service, Office of Research and Development, Biomedical Laboratory Research and Development ( NEUC-00508S – JWR ), NIH RR024888 (JWR) , VA Baltimore Research and Education Foundation (JC), The Mid-Atlantic Nutrition Obesity Research Center ( NIH P30 DK072488 ), Veterans Administration Research and Development REAP award (JWR, JC), JDRF, and ADA.

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N2 - 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.

AB - 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.

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

Abstract

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Keywords

ASJC Scopus subject areas

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