Pecina 2003 Biochim Biophys Acta

Pecina P, Capkova M, Chowdhury SKR, Drahota Z, Dubot A, Vojtiskova A, Hansikova H, Houstekova H, Zeman J, Godinot C, Houstek J (2003) Functional alteration of cytochrome c oxidase by SURF1 mutations in Leigh syndrome. Biochim. Biophys. Acta 1639: 53-63.

» PMID: 12943968

Pecina P, Capkova M, Chowdhury SKR, Drahota Z, Dubot A, Vojtiskova A, Hansikova H, Houstekova H, Zeman J, Godinot C, Houstek J (2003) Biochim. Biophys. Acta

Abstract: Subacute necrotising encephalomyopathy (Leigh syndrome) due to cytochrome c oxidase (COX) deficiency is often caused by mutations in the SURF1 gene, encoding the Surf1 protein essential for COX assembly. We have investigated five patients with different SURF1 mutations resulting in the absence of Surf1 protein. All of them presented with severe and generalised COX defect. Immunoelectrophoretic analysis of cultured fibroblasts revealed 85% decrease of the normal-size COX complexes and significant accumulation of incomplete COX assemblies of 90–120 kDa. Spectrophotometric assay of COX activity showed a 70–90% decrease in lauryl maltoside (LM)-solubilised fibroblasts. In contrast, oxygen consumption analysis in whole cells revealed only a 13–31% decrease of COX activity, which was completely inhibited by detergent in patient cells but not in controls. In patient fibroblasts ADP-stimulated respiration was 50% decreased and cytofluorometry showed a significant decrease of mitochondrial membrane potential ΔΨm in state 4, as well as a 2.4-fold higher sensitivity of ΔΨm to uncoupler. We conclude that the absence of the Surf1 protein leads to the formation of incomplete COX complexes, which in situ maintain rather high electron-transport activity, while their H₊ -pumping is impaired. Enzyme inactivation by the detergent in patient cells indicates instability of incomplete COX assemblies. • Keywords: Cytochrome c oxidase, SURF1, Leigh syndrome, Mitochondrial disorder

Labels:

Stress:Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. 

Tissue;cell: Fibroblast 

Enzyme: Complex IV; Cytochrome c Oxidase"Complex IV; Cytochrome c Oxidase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.  Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. 

HRR: Oxygraph-2k