Cytochrome c Oxidase and Mitochondrial Pathology

Abstract

On the basis of studies undertaken by MacMunn at the end of the last century, in 1924, Warburg introduced the term “Atmungsferment” to define the enzyme activity linked to cellular respiration. Simultaneously, Keilin, using spectral analysis, put forward a series of cell pigments that he named cytochromes. He had discovered the respiratory chain. In 1938, he showed that the bands associated with cytochrome a₃ were equivalent to Warburg’s “Atmungsferment” (review: Margoliash 1988). Since then, the main difficulty in understanding the mechanisms generating energy in the presence of oxygen was due to the insertion of the respiratory chain complexes, including cytochrome c oxidase (COX), inside the mitochondrial membrane. In 1961, Mitchell pro posed the chemiosmotic theory according to which the membrane is an essential component which permits the establishment of a charge separation during electron transfer. This creates a proton electrochemical potential difference between the two faces of the inner membrane. The energy of this gradient can then be used by mitochondrial ATPase-ATP synthase, embedded in the same membrane, to synthesize ATP from ADP and phosphate. In 1977, Wikström’s group studies suggested that the reduction of oxygen to water, catalyzed by COX, is accompanied by proton transfer across the membrane. These hypotheses have now been demonstrated (review: Capaldi 1990). COX, ferrocytochrome c: oxygen oxidoreductase, also called complex IV (EC 1.9.3.1) is embedded in the mitochondrial inner membrane and catalyzes the final oxidation in the respiratory chain.

Due to space limitation, the authors apologize for not being able to cite all the original articles where the discoveries were described. More often than not, references are limited to reviews where the reader can find the citations of the original work.