Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans

Cell Metabolism
Bryan L GitschlagMaulik R Patel

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.

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Related Concepts

Metazoa
DNA, Mitochondrial
Transcription, Genetic
Caenorhabditis elegans
Gene Deletion
Gene Dosage
Cosuppression
Genome, Mitochondrial
Unfolded Protein Response
Mitochondrial Fusion

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