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bioRxiv · 10.1101/2020.06.22.164475

C. elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor

Walhout, M.·Giese, G.·Walker, M.·Ponomarova, O.·Zhang, H.·Li, X.·Minevich, G.
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Abstract

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires nhr-10 and is referred to as “B12-mechanism-I”. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as “B12-mechanism-II”. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due to low dietary vitamin B12. B12-mechanism-II requires nhr-114 to activate Met/SAM cycle gene expression, the vitamin B12 transporter, pmp-5, and adjust influx and efflux of the cycle by activating msra-1 and repressing cbs-1, respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Walhout, M., Giese, G., Walker, M., Ponomarova, O., Zhang, H., Li, X., Minevich, G.. 2020-06-23. C. elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor. https://doi.org/10.1101/2020.06.22.164475

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