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.
authors: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors: Martina
authors: M
authors: Wirth
authors: Samir
authors: S
authors: Karaca
authors: Dirk
authors: D
authors: Wenzel
authors: Linh
authors: L
authors: Ho
authors: Daniel
authors: D
authors: Tishkoff
authors: David B
authors: DB
authors: Lombard
authors: Eric
authors: E
authors: Verdin
authors: Henning
authors: H
authors: Urlaub
authors: Monika
authors: M
authors: Jedrusik-Bode
authors: Wolfgang
authors: W
authors: Fischle
mesh_terms: D000107:Acetylation; D000818:Animals; D030801:Animals, Genetically Modified; D001710:Biotin / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002853:Chromatography, Liquid; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D034622:RNA Interference; D037761:Sirtuins / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D024101:Mitochondrial Proteins; D001710:Biotin; D037761:Sirtuins; D011766:Pyruvate Carboxylase
keywords: Biotin-dependent carboxylase; C. elegans; Protein acetylation; Pyruvate carboxylase; SIRT4; Sirtuins