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

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 propiona...

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Bibliographic Details
Published in:eLife 2016-07, Vol.5
Main Authors: Watson, Emma, Olin-Sandoval, Viridiana, Hoy, Michael J, Li, Chi-Hua, Louisse, Timo, Yao, Victoria, Mori, Akihiro, Holdorf, Amy D, Troyanskaya, Olga G, Ralser, Markus, Walhout, Albertha Jm
Format: Article
Language:English
Subjects:
Animals
bacteria
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - metabolism
Candida albicans
Computational and Systems Biology
Datasets
Diet
E coli
Enzymes
Gene mapping
Genes
Genes and Chromosomes
Genomes
Genomics
Health aspects
Metabolic Engineering
Metabolic Networks and Pathways - genetics
Metabolism
Metabolites
Mimicry
Mutation
Nematodes
network rewiring
Nutrient deficiency
Observations
Oxidation
propionate
Propionates - metabolism
Propionic acid
Transcription
Vitamin B 12 Deficiency
Vitamin B12
Vitamin deficiency
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.17670