Divide and conquer: how deleterious mitochondrial DNA is eliminated in the germline

Dr. Thomas Hurd
Department of Molecular Genetics University of Toronto
Thursday, November 14, 2019 - 12:00pm
McLennan Physical Laboratories, Room MP606
Invited Speaker Seminar
Unlike nuclear genomes, mitochondrial genomes undergo little recombination, are inherited only maternally, and are subject to a high mutation rate. Consequently, in order to prevent deleterious mutations from accumulating from one generation to the next, special selection mechanisms exist in the female germline. Using an allele-specific fluorescent in situ hybridization approach, we have visualized germline mtDNA selection in situ for the first time. Here, we show that mtDNA selection first manifests in the early stages of Drosophila oogenesis in differentiating germline cysts. We find that just prior, a reduction in the levels of the pro-fusion protein Mitofusin causes mitochondria to undergo a sustained period of fragmentation. This fragmented phase is necessary to isolate mitochondria preventing them from sharing their contents, which in turn reduces product complementation and allows mitochondria harboring mutant genomes to be selected against. Remarkably, not only is prolonged isolation necessary, but it is also sufficient to induce selection in somatic ovarian tissues where it otherwise does not appreciably occur. Our studies posit a generalizable mechanism to select against deleterious mtDNA mutations that may allow the development of strategies for treatment of mtDNA disorders.
Walid A. Houry
BiophysTO Lunchtime Talks