Cytochrome c oxidases generally occur as multisubunit
(multipolypeptide) complexes, the largest subunits (su I,
II and III) being relatively conserved throughout evolution.
Phylogenetic comparisons of the known archaeal
enzymes with their bacterial homologs suggest that this
enzyme existed in the common ancestor, predating the
evolution of oxygenic photosynthesis [3] and implying
that an alternative electron acceptor existed before the
occurrence of atmospheric 02. Conserved sequences of
the major subunit (su I) define a superfamily of oxidases,
known as the cytochrome c oxidase superfamily, which
includes eukaryotic and prokaryotic cytochrome c oxidases,
as well as many of the prokaryotic quinol oxidases
[4]. All members of this superfamily are redox-driven
proton pumps that generate a cross-membrane proton
gradient that is subsequently used by ATPases to catalyze
ATP synthesis. Thus, su I (and su II and III, if they are
present) are transmembrane proteins that reside in the
prokaryotic plasma membrane (which separates the cytoplasmic
and periplasmic spaces) or in the eukaryotic
mitochondrial inner membrane (which separates the
matrix and intermembrane spaces). Also, in agreement
with the endosymbiotic origin of the mitochondrion, the
three major (core) subunits (su I, II and III) of eukaryotic
cytochrome c oxidases are encoded by mitochondrial
genes. Other smaller subunits are synthesized in the
nucleus and imported into the mitochondrion.