Mitochondrial cytochromecoxidase is a key protonmotive component of the respiratory chain. Mutations in the mito-chondrially-encoded subunits of the complex have been reported in associationwith a range of diseases. In this work we used yeast and bacterial mutants to assess the effect of humanmutations insubunit 1 (L196I) andsubunit 3 (G78S, A200T,DF94–F98, F251L and W249Stop).