Respiratory adaptation in Saccharomyces cerevisiae is a complex genetic program that ensures ATP synthesis in a glucose-depleted environment. ATP is generated during respiration by the mitochondrial electron transport chain which is induced by respiratory adaptation. We have studied the terminal enzyme in mitochondrial electron transport, cytochrome c oxidase, from S. cerevisiae. Because subunits in this multisubunit enzyme are coordinately regulated, we have focused upon the well characterized subunit VI gene, COX6. In yeast, COX6 transcription is regulated by several factors thought to mediate respiratory adaptation including growth phase induction, oxygen dependence, and glucose repression. In the present study, we found that in addition to these known regulators, COX6 expression also depends upon pH and the cAMP-dependent protein kinase which may comprise additional factors signaling respiratory adaptation.