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)