Disease-related mutations in cytochrome c oxidase studied in yeast and bacterial models.

Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE

Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
Original Publication: Berlin, New York, Springer.

Mutation*; Bacterial Proteins/*metabolism ; Electron Transport Complex IV/*metabolism ; Fungal Proteins/*metabolism ; Genetic Diseases, Inborn/*enzymology; Animals ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Catalytic Domain ; Cattle ; Electron Transport Complex IV/chemistry ; Electron Transport Complex IV/genetics ; Fungal Proteins/chemistry ; Fungal Proteins/genetics ; Humans ; Mitochondria/enzymology ; Models, Molecular ; Oxidation-Reduction ; Oxygen/metabolism ; Protein Structure, Quaternary ; Protein Subunits/chemistry ; Protein Subunits/genetics ; Protein Subunits/metabolism ; Protons ; Rhodobacter sphaeroides/physiology

Mitochondrial cytochrome c oxidase is a key protonmotive component of the respiratory chain. Mutations in the mitochondrially-encoded subunits of the complex have been reported in association with a range of diseases. In this work we used yeast and bacterial mutants to assess the effect of human mutations in subunit 1 (L196I) and subunit 3 (G78S, A200T, Delta F94-F98, F251L and W249Stop). While the stop mutation at the C-terminus of subunit 3 and the short deletion were highly deleterious and abolished the assembly of the mitochondrial enzyme, the four missense mutations caused little or no effect on the respiratory function. Detailed analysis of G78S, A200T and Delta F94-F98 in Rhodobacter sphaeroides confirmed and extended these observations. We show in this study that the combination of yeast and bacterial models is a useful tool to elucidate the effect of mutations in the catalytic core of cytochrome oxidase. The yeast enzyme is highly similar to the human enzyme and provides a good model to assess the deleterious effect of reported mutations. The bacterial system allows detailed biochemical analysis of the effect of the mutations on the function and assembly of the catalytic core of the enzyme.

R01-GM56824 United States GM NIGMS NIH HHS; R37-GM26916 United States GM NIGMS NIH HHS

0 (Bacterial Proteins)
0 (Fungal Proteins)
0 (Protein Subunits)
0 (Protons)
EC 1.9.3.1 (Electron Transport Complex IV)
S88TT14065 (Oxygen)

Date Created: 20030313 Date Completed: 20030509 Latest Revision: 20220224

20240829

10.1046/j.1432-1033.2003.03482.x

12631280