Evolutionary aspects of cytochromec oxidase

Abstract

The presence of additional subunits in cytochrome oxidase distinguish the multicellular eukaryotic enzyme from that of a simple unicellular bacterial enzyme. The number of these additional subunits increases with increasing evolutionary stage of the organism. Subunits I-III of the eukaryotic enzyme are related to the three bacterial subunits, and they are encoded on mitochondrial DNA. The additional subunits are nuclear encoded. Experimental evidences are presented here to indicate that the lower enzymatic activity of the mammalian enzyme is due to the presence of nuclear-coded subunits. Dissociation of some of the nuclear-coded subunits (e.g. VIa) by laurylmaltoside and anions increased the activity of the rat liver enzyme to a value similar to that of the bacterial enzyme. Further, it is shown that the intraliposomal nucleotides influence the kinetics of ferrocytochrome c oxidation by the reconstituted enzyme from bovine heart but not from P. denitrificans. The regulatory function attributed to the nuclear-coded subunits of mammalian cytochrome c oxidase is also demonstrated by the tissue-specific response of the reconstituted enzyme from bovine heart but not from bovine liver to intraliposomal ADP. These enzymes from bovine heart and liver differ in the amino acid sequences of subunits VIa, VIIa, and VIII. The results presented here are taken to indicate a regulation of cytochrome c oxidase activity by nuclear-coded subunits which act like receptors for allosteric effectors and influence the catalytic activity of the core enzyme via conformational changes.

Coordination of metabolic plasticity in skeletal muscle

“…Furthermore, in rat liver cells, the dissociation of numerous nuclear-derived subunits results in an increase in the enzymatic activity of the COX holoenzyme (Kadenbach et al, 1991). Based on these observations, it is generally believed that these smaller proteins may play an important role in regulating the stability and maintenance of the COX holoenzyme complex (Kadenbach et al, 1991).…”

“…The existence of tissue-specific isoforms of these nuclear-encoded enzymes suggests that they may function to alter the catalytic activity of the COX complex during altered states of energy metabolism within different tissues (Kadenbach et al, 1990;Linder et al, 1995). Furthermore, in rat liver cells, the dissociation of numerous nuclear-derived subunits results in an increase in the enzymatic activity of the COX holoenzyme (Kadenbach et al, 1991). Based on these observations, it is generally believed that these smaller proteins may play an important role in regulating the stability and maintenance of the COX holoenzyme complex (Kadenbach et al, 1991).…”

Genomic insights into adaptation to high-altitude environments

“…Instead, analyses of sequence variation of subunit three of the mitochondrial COX gene (COX3) suggest that a single amino-acid substitution (Trp 116-Arg) may alter the interaction between subunits 1 (COX 1) and 3 (COX3) of the catalytic core of COX and this substitution likely contributes to the unique enzyme kinetics in barheaded geese. It is important to note that COX is a heteromeric enzyme that is composed of 10-12 subunits in birds (Kadenbach et al, 1991;Little et al, 2010). The authors only examined sequence variation in those subunits encoded by the mitochondrial genome (COX 1, 2 and 3), and hence it is still unknown whether sequence variation in nuclear-encoded COX subunits also contribute to the altered enzyme kinetics in bar-headed geese.…”

Comparison of ubiquinol and cytochrome c terminal oxidases

“…However. it is not fair to compare the bacterial E. coli cytochrome bo, complex with the mammalian au,-type oxidases as the latter oxidases are significantly more evolved containing at least 13 polypeptides [3]. Thus, in the comparisons which follow, the aa,-type cytochrome c oxidase from bacterial sources is emphasized, though data from more complex organisms are included where appropriate.…”