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

First Author  Choi J Year  2013
Journal  Biochem Biophys Res Commun Volume  435
Issue  4 Pages  671-7
PubMed ID  23688429 Mgi Jnum  J:318967
Mgi Id  MGI:6862136 Doi  10.1016/j.bbrc.2013.05.041
Citation  Choi J, et al. (2013) A novel PGC-1alpha isoform in brain localizes to mitochondria and associates with PINK1 and VDAC. Biochem Biophys Res Commun 435(4):671-7
abstractText  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.
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