Selective replication of functional mtDNA during oogenesis restricts the transmission of a deleterious mutation. Jahda H. Hill, Hong Xu. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.

   Mitochondrial DNA (mtDNA) is prone to mutation accumulation, and how organisms limit transmission of deleterious mtDNA mutations across generations remains unknown. Utilizing flies heteroplasmic for a temperature-sensitive lethal mutation in the mitochondrial gene mt:CoI, we provide evidence of selection in the female germ line, where the frequency of the mt:CoI^T300I mutation decreased at the restrictive temperature. Further, using 5-ethynyl-2-deoxyuridine (EdU) to label replicating mtDNA, we demonstrate that mtDNA replication occurs in the germarium stage of oogenesis, and concentrates around the fusome, a cytoplasmic structure mediating transport of mitochondria from somatic nurse cells to the oocyte. At the restrictive temperature, mt:CoI^T300I mitochondria are less effectively recruited to the fusome and display reduced mtDNA replication. These findings establish a previously uncharacterized developmental mechanism for selective amplification of healthy mtDNA, which may be evolutionarily conserved to prevent transmission of deleterious mutations.