Linking naturally occurring genotypic variation to the organismal phenotype is critical to our understanding of, and ability to, model biological processes such as adaptation to novel environments, disease, and aging. Rarely, however, does a simple mutation cause a single simple observable trait. Rather it is more common for a mutation to elicit an entangled web of responses. Here, we employ biochemistry as the thread to link a naturally occurring two amino acid deletion in a nuclear encoded mitochondrial protein with physiological benefits and costs in the fly Drosophila simulans. This nuclear encoded gene produces a protein that is imported into the mitochondrion and forms a subunit of complex IV (cytochrome c oxidase, or cox) of the electron transport chain. We observe that flies homozygous for the deletion have an advantage when young but pay a cost later in life. These data show that the organism responds to the deletion in a complex manner that gives insight into the mechanisms that influence mitochondrial bioenergetics and aspects of organismal physiology.