Difference between revisions of "Korsten 2010 Biochim Biophys Acta"
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{{Publication | {{Publication | ||
|title=Korsten A, de Coo IF, Spruijt L, de Wit LE, Smeets HJ, Sluiter W (2010) Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation. Biochim Biophys Acta 1797: 197-203. | |title=Korsten A, de Coo IF, Spruijt L, de Wit LE, Smeets HJ, Sluiter W (2010) Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation. Biochim Biophys Acta 1797: 197-203. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed?term=Patients%20with%20Leber%20hereditary%20optic%20neuropathy%20fail%20to%20compensate%20impaired%20oxidative%20phosphorylation PMID: 19836344] | |info=[http://www.ncbi.nlm.nih.gov/pubmed?term=Patients%20with%20Leber%20hereditary%20optic%20neuropathy%20fail%20to%20compensate%20impaired%20oxidative%20phosphorylation PMID: 19836344] | ||
|authors=Korsten A, de Coo IF, Spruijt L, de Wit LE, Smeets HJ, Sluiter W | |authors=Korsten A, de Coo IF, Spruijt L, de Wit LE, Smeets HJ, Sluiter W | ||
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|journal=Biochim Biophys Acta | |journal=Biochim Biophys Acta | ||
|abstract=Ninety-five percent of Leber hereditary optic neuropathy (LHON) patients carry a mutation in one out of three mtDNA-encoded ND subunits of complex I. Penetrance is reduced and more male than female carriers are affected. To assess if a consistent biochemical phenotype is associated with LHON expression, complex I- and complex II-dependent adenosine triphosphate synthesis rates (CI-ATP, CII-ATP) were determined in digitonin-permeabilized peripheral blood mononuclear cells (PBMCs) of thirteen healthy controls and for each primary mutation of a minimum of three unrelated patients and of three unrelated carriers with normal vision and were normalized per mitochondrion (citrate synthase activity) or per cell (protein content). We found that in mitochondria, CI-ATP and CII-ATP were impaired irrespective of the primary LHON mutation and clinical expression. An increase in mitochondrial density per cell compensated for the dysfunctional mitochondria in LHON carriers but was insufficient to result in a normal biochemical phenotype in early-onset LHON patients. | |abstract=Ninety-five percent of Leber hereditary optic neuropathy (LHON) patients carry a mutation in one out of three mtDNA-encoded ND subunits of complex I. Penetrance is reduced and more male than female carriers are affected. To assess if a consistent biochemical phenotype is associated with LHON expression, complex I- and complex II-dependent adenosine triphosphate synthesis rates (CI-ATP, CII-ATP) were determined in digitonin-permeabilized peripheral blood mononuclear cells (PBMCs) of thirteen healthy controls and for each primary mutation of a minimum of three unrelated patients and of three unrelated carriers with normal vision and were normalized per mitochondrion (citrate synthase activity) or per cell (protein content). We found that in mitochondria, CI-ATP and CII-ATP were impaired irrespective of the primary LHON mutation and clinical expression. An increase in mitochondrial density per cell compensated for the dysfunctional mitochondria in LHON carriers but was insufficient to result in a normal biochemical phenotype in early-onset LHON patients. | ||
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|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
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Revision as of 18:17, 29 February 2012
| Korsten A, de Coo IF, Spruijt L, de Wit LE, Smeets HJ, Sluiter W (2010) Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation. Biochim Biophys Acta 1797: 197-203. |
Korsten A, de Coo IF, Spruijt L, de Wit LE, Smeets HJ, Sluiter W (2010) Biochim Biophys Acta
Abstract: Ninety-five percent of Leber hereditary optic neuropathy (LHON) patients carry a mutation in one out of three mtDNA-encoded ND subunits of complex I. Penetrance is reduced and more male than female carriers are affected. To assess if a consistent biochemical phenotype is associated with LHON expression, complex I- and complex II-dependent adenosine triphosphate synthesis rates (CI-ATP, CII-ATP) were determined in digitonin-permeabilized peripheral blood mononuclear cells (PBMCs) of thirteen healthy controls and for each primary mutation of a minimum of three unrelated patients and of three unrelated carriers with normal vision and were normalized per mitochondrion (citrate synthase activity) or per cell (protein content). We found that in mitochondria, CI-ATP and CII-ATP were impaired irrespective of the primary LHON mutation and clinical expression. An increase in mitochondrial density per cell compensated for the dysfunctional mitochondria in LHON carriers but was insufficient to result in a normal biochemical phenotype in early-onset LHON patients.
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