1. Computational and Systems Biology
  2. Chromosomes and Gene Expression
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Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

  1. Albertha JM Walhout  Is a corresponding author
  2. Emma Watson
  3. Viridiana Olin-Sandoval
  4. Michael J Hoy
  5. Chi-Hua Li
  6. Timo Louisse
  7. Victoria Yao
  8. Akihiro Mori
  9. Amy D Holdorf
  10. Olga G Troyanskaya
  11. Markus Ralser
  1. University of Massachusetts Medical School, United States
  2. University of Cambridge, United Kingdom
  3. Princeton University, United States
Research Article
  • Cited 41
  • Views 4,159
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Cite this article as: eLife 2016;5:e17670 doi: 10.7554/eLife.17670

Abstract

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild.

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Author details

  1. Albertha JM Walhout

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    marian.walhout@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5587-3608

  2. Emma Watson

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Viridiana Olin-Sandoval

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  4. Michael J Hoy

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Chi-Hua Li

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Timo Louisse

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Victoria Yao

    Department of Computer Science, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3201-9983

  8. Akihiro Mori

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Amy D Holdorf

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Olga G Troyanskaya

    Department of Computer Science, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Markus Ralser

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9535-7413

Reviewing Editor

  1. Suzanne Eaton, Max Planck Institute of Molecular Cell Biology and Genetics, Germany

Publication history

  1. Received: May 11, 2016
  2. Accepted: June 20, 2016
  3. Accepted Manuscript published: July 6, 2016 (version 1)
  4. Accepted Manuscript updated: July 8, 2016 (version 2)
  5. Version of Record published: July 19, 2016 (version 3)

Copyright

© 2016, Walhout et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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