論文 - 詳細
| RRC ID | 47642 |
|---|---|
| 著者 | Gitschlag BL, Kirby CS, Samuels DC, Gangula RD, Mallal SA, Patel MR. |
| タイトル | Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans. |
| ジャーナル | Cell Metab |
| Abstract |
Mutant mitochondrial genomes (mtDNA) can be viewed as selfish genetic elements that persist in a state of heteroplasmy despite having potentially deleterious metabolic consequences. We sought to study regulation of selfish mtDNA dynamics. We establish that the large 3.1-kb deletion-bearing mtDNA variant uaDf5 is a selfish genome in Caenorhabditis elegans. Next, we show that uaDf5 mutant mtDNA replicates in addition to, not at the expense of, wild-type mtDNA. These data suggest the existence of a homeostatic copy-number control that is exploited by uaDf5 to "hitchhike" to high frequency. We also observe activation of the mitochondrial unfolded protein response (UPR(mt)) in uaDf5 animals. Loss of UPR(mt) causes a decrease in uaDf5 frequency, whereas its constitutive activation increases uaDf5 levels. UPR(mt) activation protects uaDf5 from mitophagy. Taken together, we propose that mtDNA copy-number control and UPR(mt) represent two homeostatic response mechanisms that play important roles in regulating selfish mitochondrial genome dynamics. |
| 巻・号 | 24(1) |
| ページ | 91-103 |
| 公開日 | 2016-7-12 |
| DOI | 10.1016/j.cmet.2016.06.008 |
| PII | S1550-4131(16)30294-7 |
| PMID | 27411011 |
| PMC | PMC5287496 |
| MeSH | Animals Caenorhabditis elegans / genetics* DNA, Mitochondrial / genetics Gene Deletion Gene Dosage Genome, Mitochondrial* Homeostasis / genetics* Mitochondrial Dynamics Mutation / genetics RNA Interference Transcription, Genetic Unfolded Protein Response / genetics |
| IF | 21.567 |
| 引用数 | 44 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 36 |
| 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 | atfs-1(tm4525) |