| 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
|
| リソース情報 |
| 線虫 |
atfs-1(tm4525) |
