A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster

• DOI: 10.7554/elife.16923
• Publication Date: 2016-08-01T23:59:23Z
• Authors: Maulik R Patel; Ganesh K Miriyala; Aimee J Littleton; Heiko Yang; Kien Trinh; Janet M Young; Scott R Kennedy; Yukiko M Yamashita; Leo J Pallanck; Harmit S Malik
• Keywords: Male; 0301 basic medicine; 2. Zero hunger; QH301-705.5; Science; Q; R; Mutation, Missense; mitochondrial DNA; Cell Biology; DNA, Mitochondrial; male fertility; sperm development; Electron Transport Complex IV; Mitochondrial Proteins; 03 medical and health sciences; Drosophila melanogaster; Infertility; Medicine; Animals; experimental evolution; Biology (General); lifespan; genetic suppressors

Due to their strict maternal inheritance in most animals and plants, mitochondrial genomes are predicted to accumulate mutations that are beneficial or neutral in females but harmful in males. Although a few male-harming mtDNA mutations have been identified, consistent with this ‘Mother’s Curse’, their effect on females has been largely unexplored. Here, we identify COIIG177S, a mtDNA hypomorph of cytochrome oxidase II, which specifically impairs male fertility due to defects in sperm development and function without impairing other male or female functions. COIIG177S represents one of the clearest examples of a ‘male-harming’ mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COIIG177S might specifically impair male gametogenesis. Intriguingly, some D. melanogaster nuclear genetic backgrounds can fully rescue COIIG177S -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations.