Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor
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 re...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-10-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/60259 |
| _version_ | 1811180603899379712 |
|---|---|
| author | Gabrielle E Giese Melissa D Walker Olga Ponomarova Hefei Zhang Xuhang Li Gregory Minevich Albertha JM Walhout |
| author_facet | Gabrielle E Giese Melissa D Walker Olga Ponomarova Hefei Zhang Xuhang Li Gregory Minevich Albertha JM Walhout |
| author_sort | Gabrielle E Giese |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:04:49Z |
| format | Article |
| id | doaj.art-5f1a40e24054414b90fb5d3766931b07 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:04:49Z |
| publishDate | 2020-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5f1a40e24054414b90fb5d3766931b072022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2020-10-01910.7554/eLife.60259Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptorGabrielle E Giese0https://orcid.org/0000-0002-9338-2049Melissa D Walker1Olga Ponomarova2Hefei Zhang3Xuhang Li4Gregory Minevich5Albertha JM Walhout6https://orcid.org/0000-0001-5587-3608Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United StatesProgram in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United StatesProgram in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United StatesProgram in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United StatesProgram in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United StatesDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, United StatesProgram in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United StatesVitamin 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.https://elifesciences.org/articles/60259methionine/sam cyclenuclear hormone receptorvitamin B12transcription factorsmetabolism |
| spellingShingle | Gabrielle E Giese Melissa D Walker Olga Ponomarova Hefei Zhang Xuhang Li Gregory Minevich Albertha JM Walhout Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor eLife methionine/sam cycle nuclear hormone receptor vitamin B12 transcription factors metabolism |
| title | Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor |
| title_full | Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor |
| title_fullStr | Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor |
| title_full_unstemmed | Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor |
| title_short | Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor |
| title_sort | caenorhabditis elegans methionine s adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor |
| topic | methionine/sam cycle nuclear hormone receptor vitamin B12 transcription factors metabolism |
| url | https://elifesciences.org/articles/60259 |
| work_keys_str_mv | AT gabrielleegiese caenorhabditiselegansmethioninesadenosylmethioninecycleactivityissensedandadjustedbyanuclearhormonereceptor AT melissadwalker caenorhabditiselegansmethioninesadenosylmethioninecycleactivityissensedandadjustedbyanuclearhormonereceptor AT olgaponomarova caenorhabditiselegansmethioninesadenosylmethioninecycleactivityissensedandadjustedbyanuclearhormonereceptor AT hefeizhang caenorhabditiselegansmethioninesadenosylmethioninecycleactivityissensedandadjustedbyanuclearhormonereceptor AT xuhangli caenorhabditiselegansmethioninesadenosylmethioninecycleactivityissensedandadjustedbyanuclearhormonereceptor AT gregoryminevich caenorhabditiselegansmethioninesadenosylmethioninecycleactivityissensedandadjustedbyanuclearhormonereceptor AT alberthajmwalhout caenorhabditiselegansmethioninesadenosylmethioninecycleactivityissensedandadjustedbyanuclearhormonereceptor |