title: Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone acetylation.
abstract: Dynamic acetylation and deacetylation of nuclear histones is essential for regulating the access of chromosomal DNA to transcriptional machinery. The source of acetyl-CoA for histone acetylation in mammalian cell nuclei is not clearly known. We show that acetylcarnitine formed in mitochondria, is transported into cytosol by carnitine/acylcarnitine translocase, and then enters nucleus, where it is converted to acetyl-CoA by a nuclear carnitine acetyltransferase and becomes a source of acetyl groups for histone acetylation. Genetic deficiency of the translocase markedly reduced the mitochondrial acetylcarnitine dependent nuclear histone acetylation, indicating the significance of the carnitine-dependent mitochondrial acetyl group contribution to histone acetylation.
authors.affiliation: Laboratory of Intermediary Metabolism, Clinical Research Institute of Montreal, Montreal, QC, Canada.
authors.forename: Padma
authors.initials: P
authors.lastname: Madiraju
authors.forename: Shri V
authors.initials: SV
authors.lastname: Pande
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
authors.forename: S R Murthy
authors.initials: SR
authors.lastname: Madiraju
mesh_terms: D000107:Acetylation; D000108:Acetylcarnitine / Q000378:metabolism / Q000502:physiology*; D021581:Active Transport, Cell Nucleus; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008957:Models, Genetic
chemical_list: D006657:Histones; D000108:Acetylcarnitine; D002332:Carnitine O-Acetyltransferase