Decrease of cytochrome c oxidase protein in heart mitochondria of copper-deficient rats

Copper deficiency has been reported to be associated with decreased cytochr ome c oxidase activity, which in turn may be responsible for the observed m itochondrial impairment and cardiac failure. We isolated mitochondria from hearts of copper-deficient rats: cytochrome c oxidase activity was found to be lower than in copper-adequate mitochondria, The residual activity paral leled copper content of mitochondria and also corresponded with the heme am ount associated with cytochrome aa3, In fact, lower absorption in the at-ba nd region of cytochrome aa3 was found for copper-deficient rat heart mitoch ondria, Gel electrophoresis of protein extracted from mitochondrial membran es allowed measurements of protein content of the complexes of oxidative ph osphorylation, revealing a lower content of complex IV protein in copper-de ficient rat heart mitochondria, The alterations caused by copper deficiency appear to be specific for cytochrome c oxidase. Changes were not observed for F(0)F(1)ATP synthase activity, for heme contents of cytochrome c and b, and for protein contents of complexes I, III and V, The present study demo nstrates that the alteration of cytochrome c oxidase activity observed in c opper deficiency is due to a diminished content of assembled protein and th at shortness of copper impairs heme insertion into cytochrome c oxidase.