Biotin starvation causes mitochondrial protein hyperacetylation and partial rescue by the SIRT3-like deacetylase Hst4p

• Published in: Nature communications Vol. 6; no. 1; p. 7726
• Main Authors: Madsen, Christian T., Sylvestersen, Kathrine B., Young, Clifford, Larsen, Sara C., Poulsen, Jon W., Andersen, Marianne A., Palmqvist, Eva A., Hey-Mogensen, Martin, Jensen, Per B., Treebak, Jonas T., Lisby, Michael, Nielsen, Michael L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.07.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 14/35; 14/63; 38/1; 38/70; 631/80/458/1275; 692/699/317; 82/16; 82/58; Acetyl Coenzyme A - metabolism; Acetylation; Biotin; Biotin - deficiency; Biotin - metabolism; Cell Respiration; Energy Metabolism; Health sciences; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Homeostasis; Humanities and Social Sciences; Mass Spectrometry; Metabolic disorders; Metabolism; Metabolites; Microscopy, Fluorescence; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; multidisciplinary; Mutation; NAD - metabolism; Niacinamide - metabolism; Organisms, Genetically Modified; Oxygen Consumption; Physiology; Prostheses; Proteins; Proteomics; Reactive Oxygen Species - metabolism; Respiration; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Starvation; Yeast; Yeasts; Denmark
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8726

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. Biotin is an essential vitamin in the regulation of energy metabolism. Here Madsen et al. show that biotin deficiency in yeast leads to hyperacetylation of mitochondrial proteins that is compensated for by the SIRT-like deacetylase Hst4p.