期刊
CELL METABOLISM
卷 24, 期 1, 页码 91-103出版社
CELL PRESS
DOI: 10.1016/j.cmet.2016.06.008
关键词
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资金
- Helen Hay Whitney Foundation Fellowship
- Mathers Foundation
- HHMI
- Vanderbilt University
- NIH-sponsored Cellular, Biochemical and Molecular Sciences Training Program [5T32GM008554-18]
- NIH-funded Tennessee Center for AIDS Research [P30 AI110527]
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.
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