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

Martina Wirth, Samir Karaca, Dirk Wenzel, Linh Ho, Daniel Tishkoff, David B. Lombard, Eric Verdin, Henning Urlaub, Monika Jedrusik-Bode*, Wolfgang Fischle

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)705-720
Number of pages16
Issue number6
StatePublished - Nov 2013
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. Robert Janke (Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering group, Magdeburg) for help in setting up plate reader based pyruvate carboxylase activity assays and Jennifer Seefeldt for help in subcellular fractionations. The anti-PC antibodies were a gift from Drs. Sarawut Jitrapakdee (Mahidol University) and John C. Wallace (University of Adelaide). We acknowledge further the CGC and NBRP for providing C. elegans strains. We are thankful to Drs. Dmitry Agafonov and Timur Samatov for wheat germ extract protein expression, Dr. Nora Koester-Eiserfunke for support in C. elegans work and Drs. Henriette Franz, Kerstin Mosch and Szabolcs Sörös for help with the statistical program R, cell culture and biochemical techniques. This work was supported by the Max Planck Society (WF) , the DFG ( JE 505/ 1-2, MJB ), an NIA training grant ( T32-AG000114, DT ), the NIH ( 1R01GM101171 , DBL), the Ellison Medical Foundation ( AG-NS-0583-09 , DBL), the NIDDK ( DK085610 , EV) and the Gladstone Institutes (EV).


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

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology


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