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Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans

Gitschlag, B.L., Kirby, C.S., Samuels, D.C., Gangula, R.D., Mallal, S.A. and Patel, M.R. (2016) Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans. Cell Metabolism, 24 (1). pp. 91-103.

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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 (UPRmt) in uaDf5 animals. Loss of UPRmt causes a decrease in uaDf5 frequency, whereas its constitutive activation increases uaDf5 levels. UPRmt activation protects uaDf5 from mitophagy. Taken together, we propose that mtDNA copy-number control and UPRmt represent two homeostatic response mechanisms that play important roles in regulating selfish mitochondrial genome dynamics.

Publication Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: Elsevier
Copyright: © 2016 Elsevier Inc.
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