REVIEW: Mechanisms of Intracellular Selection of Mitochondrial DNA

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Georgii Muravyov^1,2 and Dmitry A. Knorre^2,a*

¹Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia

²A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

^* To whom correspondence should be addressed.

Received: September 23, 2025; Revised: November 15, 2025; Accepted: November 20, 2025

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Eukaryotic cells contain multiple mitochondrial DNA (mtDNA) molecules. Heteroplasmy is coexistence in the same cell of different mtDNA variants competing for cellular resources required for their replication. Here, we review documented cases of emergence and spread of selfish mtDNA (i.e., mtDNA that has a selective advantage in a cell but decreases cell fitness) in eukaryotic species, from humans to baker’s yeast. The review discusses hypothetical mechanisms enabling preferential proliferation of certain mtDNA variants in heteroplasmy. We propose that selfish mtDNAs have significantly influenced the evolution of eukaryotes and may be responsible for the emergence of uniparental inheritance and constraints on the mtDNA copy number in germline cells.

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KEY WORDS: mitochondrial DNA, mtDNA quality control, mitophagy, heteroplasmy, intracellular selection, selfish gene

DOI: 10.1134/S0006297925603296

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