title: Biotin starvation causes mitochondrial protein hyperacetylation and partial rescue by the SIRT3-like deacetylase Hst4p.
abstract: The essential vitamin biotin is a covalent and tenaciously attached prosthetic group in several carboxylases that play important roles in the regulation of energy metabolism. Here we describe increased acetyl-CoA levels and mitochondrial hyperacetylation as downstream metabolic effects of biotin deficiency. Upregulated mitochondrial acetylation sites correlate with the cellular deficiency of the Hst4p deacetylase, and a biotin-starvation-induced accumulation of Hst4p in mitochondria supports a role for Hst4p in lowering mitochondrial acetylation. We show that biotin starvation and knockout of Hst4p cause alterations in cellular respiration and an increase in reactive oxygen species (ROS). These results suggest that Hst4p plays a pivotal role in biotin metabolism and cellular energy homeostasis, and supports that Hst4p is a functional yeast homologue of the sirtuin deacetylase SIRT3. With biotin deficiency being involved in various metabolic disorders, this study provides valuable insight into the metabolic effects biotin exerts on eukaryotic cells.
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Madsen
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Kathrine B
authors.initials: KB
authors.lastname: Sylvestersen
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Clifford
authors.initials: C
authors.lastname: Young
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Larsen
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Jon W
authors.initials: JW
authors.lastname: Poulsen
authors.affiliation: Section of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Marianne A
authors.initials: MA
authors.lastname: Andersen
authors.affiliation: Department of Yeast Physiology and Cultivation, Novo Nordisk A/S, Novo Nordisk park 1, DK-2760 Måløv, Denmark.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Palmqvist
authors.affiliation: Department of Obesity Biology, Novo Nordisk A/S, Novo Nordisk park 1, DK-2760 Måløv, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Hey-Mogensen
authors.affiliation: Department of Obesity Biology, Novo Nordisk A/S, Novo Nordisk park 1, DK-2760 Måløv, Denmark.
authors.forename: Per B
authors.initials: PB
authors.lastname: Jensen
authors.affiliation: Section of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Treebak
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaloees Vej 5, DK-2200 Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Lisby
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nielsen
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000107:Acetylation; D001710:Biotin / Q000172:deficiency / Q000378:metabolism*; D019069:Cell Respiration; D004734:Energy Metabolism; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D030781:Organisms, Genetically Modified; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013217:Starvation
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D009243:NAD; D009536:Niacinamide; D001710:Biotin; D000105:Acetyl Coenzyme A; C512518:Hst4 protein, S cerevisiae; D006655:Histone Deacetylases