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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 COII G177S , 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. COII G177S  represents one of the clearest examples of a ‘male-harming’ mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COII G177S  might specifically impair male gametogenesis. Intriguingly, some  D. melanogaster  nuclear genetic backgrounds can fully rescue COII G177S  -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations.

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