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- Title
Caenorhabditis elegans methionine/Sadenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor.
- Authors
Giese, Gabrielle E.; Walker, Melissa D.; Ponomarova, Olga; Hefei Zhang; Xuhang Li; Minevich, Gregory; Walhout, Albertha J. M.
- 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.
- Subjects
CAENORHABDITIS elegans; NUCLEAR receptors (Biochemistry); VITAMIN B12; METHIONINE
- Publication
eLife, 2020, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.60259