Pecina 2004 Am J Physiol Cell Physiol: Difference between revisions
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|year=2004 | |year=2004 | ||
|journal=Am J Physiol Cell Physiol | |journal=Am J Physiol Cell Physiol | ||
|abstract=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 (P<sub>O2</sub>) at half-maximal respiration rate (P<sub>50</sub>) in intact coupled cells and in digitonin-permeabilized uncoupled cells. In both cases, the P<sub>50</sub> 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 P<sub>O2</sub>, the depressed oxygen affinity may lead in vivo to limitations of respiration, resulting in impaired energy provision in Leigh syndrome patients. | |abstract=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 (P<sub>O2</sub>) at half-maximal respiration rate (P<sub>50</sub>) in intact coupled cells and in digitonin-permeabilized uncoupled cells. In both cases, the P<sub>50</sub> 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 P<sub>O2</sub>, the depressed oxygen affinity may lead ''in vivo'' to limitations of respiration, resulting in impaired energy provision in Leigh syndrome patients. | ||
|keywords=Oxygen kinetics, Mitochondrial disease | |keywords=Oxygen kinetics, Mitochondrial disease | ||
|mipnetlab= | |mipnetlab=AT Innsbruck Gnaiger E, CZ Prague Zeman J, CZ Prague Houstek J | ||
|discipline=Mitochondrial Physiology, Biomedicine | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} |
Revision as of 12:47, 20 March 2015
Pecina P, Gnaiger E, Zeman J, Pronicka E, Houstek J (2004) Decreased affinity to oxygen of cytochrome c oxidase in Leigh syndrome caused by SURF1 mutations. Am J Physiol Cell Physiol 287:C1384-8. |
Pecina P, Gnaiger E, Zeman J, Pronicka E, Houstek J (2004) Am J Physiol Cell Physiol
Abstract: 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. โข Keywords: Oxygen kinetics, Mitochondrial disease
โข O2k-Network Lab: AT Innsbruck Gnaiger E, CZ Prague Zeman J, CZ Prague Houstek J
Labels: MiParea: Respiration, nDNA;cell genetics, mt-Medicine, Patients
Pathology: Inherited
Organism: Human
Preparation: Intact cells Enzyme: Complex IV;cytochrome c oxidase Regulation: O2"O2" 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. Coupling state: ROUTINE
HRR: Oxygraph-2k