title: Cytoplasmic sequestration of HDAC7 from mitochondrial and nuclear compartments upon initiation of apoptosis.
abstract: Control of global histone acetylation status is largely governed by the opposing enzymatic activities of histone acetyltransferases and deacetylases (HDACs). HDACs were originally identified as modulators of nuclear histone acetylation status and have been linked to chromosomal condensation and subsequent gene repression. Accumulating evidence highlights HDAC modification of non-histone targets. Mitochondria were first characterized as intracellular organelles responsible for energy production through the coupling of oxidative phosphorylation to respiration. More recently, mitochondria have been implicated in programmed cell death whereby release of pro-apoptotic inner membrane space factors facilitates apoptotic progression. Here we describe the novel discovery that the nuclear encoded Class II human histone deacetylase HDAC7 localizes to the mitochondrial inner membrane space of prostate epithelial cells and exhibits cytoplasmic relocalization in response to initiation of the apoptotic cascade. These results highlight a previously unrecognized link between HDACs, mitochondria, and programmed cell death.
authors.affiliation: Division of Radiation Research, Department of Radiation Medicine, Lombardi Comprehensive Cancer Canter, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Bakin
authors.forename: Mira O
authors.initials: MO
authors.lastname: Jung
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D017209:Apoptosis; D015153:Blotting, Western; D020134:Catalytic Domain; D002467:Cell Nucleus / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
chemical_list: D006657:Histones; D049452:Green Fluorescent Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C543273:HDAC7 protein, human; D006655:Histone Deacetylases; D010100:Oxygen