Cytochrome c Oxidase-deficient Patients Have Distinct Subunit Assembly Profiles

Bonnie J. Hanson, Rosalba Carrozzo, Fiorella Piemonte, Alessandra Tessa, Brian H. Robinson, Roderick A. Capaldi

Research output: Contribution to journalArticlepeer-review


Cytochrome c oxidase (COX) deficiency is the most common respiratory chain defect in childhood and is clinically heterogeneous. We report a study of six patients with COX deficiencies. Two of the patients had as yet undefined defects, three patients had Surf-1 mutations, and one patient had a 15-base pair deletion in the COX III subunit. We show that quantitative measurements of steady-state levels of subunits by monoclonal antibody reactivity, when used in combination with a discontinuous sucrose gradient methods, provide an improved diagnosis of COX deficiencies by distinguishing between kinetic, stability, and assembly defects. The two mutants of undefined etiology had a full complement of subunits with one stable and the other partially unstable to detergent solubilization. Both are likely to carry mutations in nuclear-encoded subunits of the complex. The three Surf-1 mutants and the COX III mutant each had reduced steady-state levels of subunits but variable associations of the residual subunits. This information, as well as aiding in diagnosis, helps in understanding the genotype-phenotype relationships of COX deficiencies and provides insight into the mechanism of assembly of the enzyme complex.

Original languageEnglish
Pages (from-to)16296-16301
Number of pages6
JournalJournal of Biological Chemistry
Issue number19
Publication statusPublished - May 11 2001

ASJC Scopus subject areas

  • Biochemistry


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