論文 - 詳細
| RRC ID | 75626 |
|---|---|
| 著者 | Ponomarova O, Zhang H, Li X, Nanda S, Leland TB, Fox BW, Starbard AN, Giese GE, Schroeder FC, Yilmaz LS, Walhout AJM. |
| タイトル | A D-2-hydroxyglutarate dehydrogenase mutant reveals a critical role for ketone body metabolism in Caenorhabditis elegans development. |
| ジャーナル | PLoS Biol |
| Abstract |
In humans, mutations in D-2-hydroxyglutarate (D-2HG) dehydrogenase (D2HGDH) result in D-2HG accumulation, delayed development, seizures, and ataxia. While the mechanisms of 2HG-associated diseases have been studied extensively, the endogenous metabolism of D-2HG remains unclear in any organism. Here, we find that, in Caenorhabditis elegans, D-2HG is produced in the propionate shunt, which is transcriptionally activated when flux through the canonical, vitamin B12-dependent propionate breakdown pathway is perturbed. Loss of the D2HGDH ortholog, dhgd-1, results in embryonic lethality, mitochondrial defects, and the up-regulation of ketone body metabolism genes. Viability can be rescued by RNAi of hphd-1, which encodes the enzyme that produces D-2HG or by supplementing either vitamin B12 or the ketone bodies 3-hydroxybutyrate (3HB) and acetoacetate (AA). Altogether, our findings support a model in which C. elegans relies on ketone bodies for energy when vitamin B12 levels are low and in which a loss of dhgd-1 causes lethality by limiting ketone body production. |
| 巻・号 | 21(4) |
| ページ | e3002057 |
| 公開日 | 2023-4-1 |
| DOI | 10.1371/journal.pbio.3002057 |
| PII | PBIOLOGY-D-22-01380 |
| PMID | 37043428 |
| PMC | PMC10096224 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Humans Ketones Propionates* / metabolism Vitamin B 12 |
| IF | 7.076 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 21 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm6671 |