Mutations in the gene SURF1 prevent synthesis of cytochrome-c oxidase (COX)-specific assembly protein and result in a fatal neurological disorder, Leigh syndrome. Because this severe COX deficiency presents with barely detectable changes of cellular respiratory rates under normoxic conditions, we analyzed the respiratory response to low oxygen in cultured fibroblasts harboring SURF1 mutations with high-resolution respirometry. The oxygen kinetics was quantified by the partial pressure of oxygen (PO2) at half-maximal respiration rate (P50) in intact coupled cells and in digitonin-permeabilized uncoupled cells. In both cases, the P50 in patients was elevated 2.1- and 3.3-fold, respectively, indicating decreased affinity of COX for oxygen. These results suggest that at physiologically low intracellular PO2, the depressed oxygen affinity may lead in vivo to limitations of respiration, resulting in impaired energy provision in Leigh syndrome patients.

• MeSH
• deficit cytochrom-c-oxidázy genetika   metabolismus   patofyziologie   MeSH
• fibroblasty metabolismus   MeSH
• kultivované buňky MeSH
• kyslík metabolismus   MeSH
• Leighova nemoc genetika   metabolismus   patofyziologie   MeSH
• lidé MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• mutace MeSH
• proteiny genetika   MeSH
• respirační komplex IV metabolismus   MeSH
• spotřeba kyslíku fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyslík MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• proteiny MeSH
• respirační komplex IV MeSH
• Surf-1 protein MeSH Prohlížeč