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


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.

SUBMITTER: Giese GE 

PROVIDER: S-EPMC7561351 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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<i>Caenorhabditis elegans</i> methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor.

Giese Gabrielle E GE   Walker Melissa D MD   Ponomarova Olga O   Zhang Hefei H   Li Xuhang X   Minevich Gregory G   Walhout Albertha Jm AJ  

eLife 20201005


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 <i>Caenorhabditis elegans,</i> 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 <i>nhr-10</i> and is referred to as 'B12-mechanis  ...[more]

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