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Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA.

Authors
  • Karavaeva, Iuliia E1
  • Golyshev, Sergey A2
  • Smirnova, Ekaterina A2
  • Sokolov, Svyatoslav S2
  • Severin, Fedor F2
  • Knorre, Dmitry A3
  • 1 Faculty of Bioengineering and Bioinformatics, Moscow State University, Leninskiye Gory 1-73, Moscow 119991, Russia.
  • 2 Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskiye Gory 1-40, Moscow 119991, Russia.
  • 3 Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskiye Gory 1-40, Moscow 119991, Russia [email protected]
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Apr 01, 2017
Volume
130
Issue
7
Pages
1274–1284
Identifiers
DOI: 10.1242/jcs.197269
PMID: 28193734
Source
Medline
Keywords
License
Unknown

Abstract

Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the ultimate variant of mtDNA present depends on their relative replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild-type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild-type mtDNA. This effect was significantly lower in cells with disrupted mitochondria fission or repression of the autophagy-related genes ATG8, ATG32 or ATG33, implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization. Moreover, the rate of mitochondrially targeted GFP turnover was higher in zygotes treated with uncoupler than in haploid cells or untreated zygotes. Finally, we showed that vacuoles of zygotes with uncoupler-activated autophagy contained DNA. Taken together, our data demonstrate that mitochondrial depolarization inhibits clonal expansion of selfish mtDNA and this effect depends on mitochondrial fission and autophagy. These observations suggest an activation of mitochondria quality control mechanisms in heteroplasmic yeast zygotes.

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