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

TitleMetabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans.
Publication TypeJournal Article
Year of Publication2016
AuthorsWatson, E, Olin-Sandoval, V, Hoy, MJ, Li, C-H, Louisse, T, Yao, V, Mori, A, Holdorf, AD, Troyanskaya, OG, Ralser, M, Walhout, AJm
JournalElife
Volume5
Date Published2016 Jul 06
ISSN2050-084X
KeywordsAnimals, Caenorhabditis elegans, Metabolic Engineering, Metabolic Networks and Pathways, Propionates, Vitamin B 12 Deficiency
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.

DOI10.7554/eLife.17670
Alternate JournalElife
PubMed ID27383050
PubMed Central IDPMC4951191
Grant ListP40 OD010440 / OD / NIH HHS / United States
R01 DK068429 / DK / NIDDK NIH HHS / United States
R01 GM071966 / GM / NIGMS NIH HHS / United States
R01 HG005998 / HG / NHGRI NIH HHS / United States
T32 HG003284 / HG / NHGRI NIH HHS / United States