Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone acetylation.
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.
Madiraju
Padma
P
Laboratory of Intermediary Metabolism, Clinical Research Institute of Montreal, Montreal, QC, Canada.
Pande
Shri V
SV
Prentki
Marc
M
Madiraju
S R Murthy
SR
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
D006657:Histones; D000108:Acetylcarnitine; D002332:Carnitine O-Acetyltransferase