@article{9ab99b13f4a0449d8ebd4cfb4b91a4c9,
title = "Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases",
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",
author = "Martina Wirth and Samir Karaca and Dirk Wenzel and Linh Ho and Daniel Tishkoff and Lombard, {David B.} and Eric Verdin and Henning Urlaub and Monika Jedrusik-Bode and Wolfgang Fischle",
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 S{\"o}r{\"o}s 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).",
year = "2013",
month = nov,
doi = "10.1016/j.mito.2013.02.002",
language = "English (US)",
volume = "13",
pages = "705--720",
journal = "Mitochondrion",
issn = "1567-7249",
publisher = "Elsevier",
number = "6",
}