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

doi:10.1016/j.mito.2013.02.002

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 journal › Article › peer-review

15 Scopus citations

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.

Original language	English (US)
Pages (from-to)	705-720
Number of pages	16
Journal	Mitochondrion
Volume	13
Issue number	6
DOIs	https://doi.org/10.1016/j.mito.2013.02.002
State	Published - Nov 2013
Externally published	Yes

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).

Keywords

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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10.1016/j.mito.2013.02.002

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Wirth, M., Karaca, S., Wenzel, D., Ho, L., Tishkoff, D., Lombard, D. B., Verdin, E., Urlaub, H., Jedrusik-Bode, M., & Fischle, W. (2013). Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases. Mitochondrion, 13(6), 705-720. https://doi.org/10.1016/j.mito.2013.02.002

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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).",

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doi = "10.1016/j.mito.2013.02.002",

language = "English (US)",

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Wirth, M, Karaca, S, Wenzel, D, Ho, L, Tishkoff, D, Lombard, DB, Verdin, E, Urlaub, H, Jedrusik-Bode, M & Fischle, W 2013, 'Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases', Mitochondrion, vol. 13, no. 6, pp. 705-720. https://doi.org/10.1016/j.mito.2013.02.002

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T1 - Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases

AU - Wirth, Martina

AU - Karaca, Samir

AU - Wenzel, Dirk

AU - Ho, Linh

AU - Tishkoff, Daniel

AU - Lombard, David B.

AU - Verdin, Eric

AU - Urlaub, Henning

AU - Jedrusik-Bode, Monika

AU - Fischle, Wolfgang

N1 - 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).

PY - 2013/11

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N2 - 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.

AB - 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.

KW - Biotin-dependent carboxylase

KW - C. elegans

KW - Protein acetylation

KW - Pyruvate carboxylase

KW - SIRT4

KW - Sirtuins

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DO - 10.1016/j.mito.2013.02.002

M3 - Article

C2 - 23438705

AN - SCOPUS:84887015551

SN - 1567-7249

VL - 13

SP - 705

EP - 720

JO - Mitochondrion

JF - Mitochondrion

IS - 6

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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