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Elife. 2016 Jul 6;5. pii: e17670. doi: 10.7554/eLife.17670.

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans.

Author information

1
Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States.
2
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
3
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
4
Department of Computer Science, Princeton University, Princeton, United States.
5
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States.
6
Simons Center for Data Analysis, Simons Foundation, New York, United States.
7
The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.

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.

KEYWORDS:

C. elegans; bacteria; chromosomes; computational biology; genes; human; metabolism; network rewiring; propionate; systems biology; transcription; vitamin B12

PMID:
27383050
PMCID:
PMC4951191
DOI:
10.7554/eLife.17670
[Indexed for MEDLINE]
Free PMC Article

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