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.
authors.affiliation: Department of Neurology, University of Maryland, Baltimore, MD 21201, USA. jochoi@som.umaryland.edu
authors.forename: Joungil
authors.initials: J
authors.lastname: Choi
authors.forename: Vera Venkatanaresh Kumar
authors.initials: VV
authors.lastname: Batchu
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert
authors.forename: Rudolph J
authors.initials: RJ
authors.lastname: Castellani
authors.forename: James W
authors.initials: JW
authors.lastname: Russell
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020033:Protein Isoforms / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020033:Protein Isoforms; D011494:Protein Kinases; D015534:Trans-Activators; D014157:Transcription Factors; D050994:Voltage-Dependent Anion Channels; D000099202:PTEN-Induced Putative Kinase; C485290:Ppargc1a protein, mouse