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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)671-677
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume435
Issue number4
DOIs
StatePublished - Jun 14 2013

Keywords

  • Brain
  • Mitochondria
  • PGC-1α
  • PINK1
  • VDAC

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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