Journal article
Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans
Cell Metabolism, Vol.24(1), pp.91-103
2016
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 (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.
Details
- Title
- Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans
- Authors/Creators
- B.L. Gitschlag (Author/Creator) - Vanderbilt UniversityC.S. Kirby (Author/Creator) - Vanderbilt UniversityD.C. Samuels (Author/Creator) - Vanderbilt UniversityR.D. Gangula (Author/Creator) - Vanderbilt UniversityS.A. Mallal (Author/Creator) - Vanderbilt UniversityM.R. Patel (Author/Creator) - Vanderbilt University
- Publication Details
- Cell Metabolism, Vol.24(1), pp.91-103
- Publisher
- Elsevier
- Identifiers
- 991005542102407891
- Copyright
- © 2016 Elsevier Inc.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.197 Molecular & Cell Biology - Mitochondria
- 1.197.564 Mitochondrial Function
- Web Of Science research areas
- Cell Biology
- Endocrinology & Metabolism
- ESI research areas
- Molecular Biology & Genetics