2. Academic Validation
  3. Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases

Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases

  • Mitochondrion. 2013 Nov;13(6):705-20. doi: 10.1016/j.mito.2013.02.002.
Martina Wirth 1,  Samir Karaca,  Dirk Wenzel,  Linh Ho,  Daniel Tishkoff,  David B Lombard,  Eric Verdin,  Henning Urlaub,  Monika Jedrusik-Bode,  Wolfgang Fischle
Affiliations

Affiliation

  • 1 Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
PMID: 23438705 DOI: 10.1016/j.mito.2013.02.002
Abstract

The biological and enzymatic function of SIRT4 is largely uncharacterized. We show that the Caenorhabditis elegans SIR-2.2 and SIR-2.3 orthologs of SIRT4 are ubiquitously expressed, also localize to mitochondria and function during oxidative stress. Further, we identified conserved interaction with mitochondrial biotin-dependent carboxylases (PC, PCC, MCCC), key enzymes in anaplerosis and ketone body formation. The carboxylases were found acetylated on multiple lysine residues and detailed analysis of mPC suggested that one of these residues, K748ac, might regulate enzymatic activity. Nevertheless, no changes in mPC acetylation levels and enzymatic activity could be detected upon overexpression or loss of functional SIRT4.

Keywords

Biotin-dependent carboxylase; C. elegans; Protein acetylation; Pyruvate carboxylase; SIRT4; Sirtuins.

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