Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Commun. 2015 Jul 9;6:7726. doi: 10.1038/ncomms8726.

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

Author information

1
Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
2
Section of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
3
Department of Yeast Physiology and Cultivation, Novo Nordisk A/S, Novo Nordisk park 1, DK-2760 Måløv, Denmark.
4
Department of Obesity Biology, Novo Nordisk A/S, Novo Nordisk park 1, DK-2760 Måløv, Denmark.
5
Department of Biology, University of Copenhagen, Ole Maaloees Vej 5, DK-2200 Copenhagen, Denmark.

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.

PMID:
26158509
PMCID:
PMC4510963
DOI:
10.1038/ncomms8726
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center