title: Depression of mitochondrial metabolism by downregulation of cytoplasmic deacetylase, HDAC6.
abstract: Mitochondria perform multiple functions critical to the maintenance of cellular homeostasis. Here we report that the downregulation of histone deacetylase 6 (HDAC6) causes a reduction in the net activity of mitochondrial enzymes, including respiratory complex II and citrate synthase. HDAC6 deacetylase and ubiquitin-binding activities were both required for recovery of reduced mitochondrial metabolic activity due to the loss of HDAC6. Hsp90, a substrate of HDAC6, localizes to mitochondria and partly mediates the regulation of mitochondrial metabolic activity by HDAC6. Our finding suggests that HDAC6 regulates mitochondrial metabolism and might serve as a cellular homeostasis surveillance factor.
authors.affiliation: Department of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, Japan. k_kamemura@nagahama-i-bio.ac.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kamemura
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Ogawa
authors.forename: Saki
authors.initials: S
authors.lastname: Ohkubo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ohtsuka
authors.forename: Yu
authors.initials: Y
authors.lastname: Shitara
authors.forename: Tohru
authors.initials: T
authors.lastname: Komiya
authors.forename: Satoko
authors.initials: S
authors.lastname: Maeda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000172:deficiency / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*
chemical_list: C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases