論文 - 詳細
| RRC ID | 65211 |
|---|---|
| 著者 | Amin MR, Mahmud SA, Dowgielewicz JL, Sapkota M, Pellegrino MW. |
| タイトル | A novel gene-diet interaction promotes organismal lifespan and host protection during infection via the mitochondrial UPR. |
| ジャーナル | PLoS Genet |
| Abstract |
Cells use a variety of mechanisms to maintain optimal mitochondrial function including the mitochondrial unfolded protein response (UPRmt). The UPRmt mitigates mitochondrial dysfunction by differentially regulating mitoprotective gene expression through the transcription factor ATFS-1. Since UPRmt activation is commensurate with organismal benefits such as extended lifespan and host protection during infection, we sought to identify pathways that promote its stimulation. Using unbiased forward genetics screening, we isolated novel mutant alleles that could activate the UPRmt. Interestingly, we identified one reduction of function mutant allele (osa3) in the mitochondrial ribosomal gene mrpl-2 that activated the UPRmt in a diet-dependent manner. We find that mrpl-2(osa3) mutants lived longer and survived better during pathogen infection depending on the diet they were fed. A diet containing low levels of vitamin B12 could activate the UPRmt in mrpl-2(osa3) animals. Also, we find that the vitamin B12-dependent enzyme methionine synthase intersects with mrpl-2(osa3) to activate the UPRmt and confer animal lifespan extension at the level of ATFS-1. Thus, we present a novel gene-diet pairing that promotes animal longevity that is mediated by the UPRmt. |
| 巻・号 | 16(12) |
| ページ | e1009234 |
| 公開日 | 2020-12-1 |
| DOI | 10.1371/journal.pgen.1009234 |
| PII | PGENETICS-D-20-00171 |
| PMID | 33338044 |
| PMC | PMC7781476 |
| MeSH | 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / metabolism Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Diet* Disease Resistance* Gene-Environment Interaction Genotype* Longevity* Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Pseudomonas Infections / immunology Transcription Factors / genetics Transcription Factors / metabolism Unfolded Protein Response* Vitamin B 12 / metabolism |
| リソース情報 | |
| 線虫 | tm4525 |