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

Alex Korsten, Irenaeus F M de Coo, Liesbeth Spruijt, L. Elly A. de Wit, Hubert J. M. Smeets, Wim Sluiter*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)197-203
JournalBiochimica et Biophysica Acta-bioenergetics
Issue number2
Publication statusPublished - Feb 2010


  • Biochemical phenotype
  • Leber hereditary optic neuropathy
  • Mitochondrial density
  • Oxidative phosphorylation
  • Peripheral blood mononuclear cell

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