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

Nat Commun. 2015 Jul 9:6:7726. doi: 10.1038/ncomms8726.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A / metabolism*
  • Acetylation
  • Biotin / deficiency
  • Biotin / metabolism*
  • Cell Respiration
  • Energy Metabolism
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Homeostasis
  • Mass Spectrometry
  • Microscopy, Fluorescence
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • NAD / metabolism
  • Niacinamide / metabolism
  • Organisms, Genetically Modified
  • Oxygen Consumption
  • Reactive Oxygen Species / metabolism*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Starvation

Substances

  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Saccharomyces cerevisiae Proteins
  • NAD
  • Niacinamide
  • Biotin
  • Acetyl Coenzyme A
  • Hst4 protein, S cerevisiae
  • Histone Deacetylases