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. Epub 2013 Feb 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Animals, Genetically Modified
  • Biotin / metabolism*
  • Caenorhabditis elegans / metabolism*
  • Chromatography, Liquid
  • HEK293 Cells
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Oxidative Stress
  • Pyruvate Carboxylase / metabolism*
  • RNA Interference
  • Sirtuins / metabolism*
  • Tandem Mass Spectrometry


  • Mitochondrial Proteins
  • Biotin
  • Sirtuins
  • Pyruvate Carboxylase