title: The hitchhiker's guide to PGC-1α isoform structure and biological functions.
abstract: Proteins of the peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1 (PGC-1) family of transcriptional coactivators coordinate physiological adaptations in many tissues, usually in response to demands for higher nutrient and energy supply. Of the founding members of the family, PGC-1α (also known as PPARGC1A) is the most highly regulated gene, using multiple promoters and alternative splicing to produce a growing number of coactivator variants. PGC-1α promoters are selectively active in distinct tissues in response to specific stimuli. To date, more than ten novel PGC-1α isoforms have been reported to be expressed from a novel promoter (PGC-1α-b, PGC-1α-c), to undergo alternative splicing (NT-PGC-1α) or both (PGC-1α2, PGC-1α3, PGC-1α4). The resulting proteins display differential regulation and tissue distribution and, most importantly, exert specific biological functions. In this review we discuss the structural and functional characteristics of the novel PGC-1α isoforms, aiming to provide an integrative view of this constantly expanding system of transcriptional coactivators.
authors.affiliation: Molecular and Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, SE-17177, Stockholm, Sweden.
authors.forename: Vicente
authors.initials: V
authors.lastname: Martínez-Redondo
authors.forename: Amanda T
authors.initials: AT
authors.lastname: Pettersson
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Ruas
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000737:chemistry; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry*; D015533:Transcriptional Activation
chemical_list: D018076:DNA, Complementary; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C501429:Ppargc1a protein, rat; D020033:Protein Isoforms; D014157:Transcription Factors