Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation

A Korsten, IFM Coo, L Spruijt, Elly Wit, HJM Smeets, Wim Sluiter

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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 mate 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. (C) 2009 Elsevier B.V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)197-203
Number of pages7
JournalBiochimica et Biophysica Acta-Bioenergetics
Volume1797
Issue number2
DOIs
Publication statusPublished - 2010

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