Background: MNGIE syndrome (mitochondrial neurogastrointestinal encephalopathy) is caused by mutations in the thymidine phosphorylase (TP) gene. It is characterized by progressive external ophthalmoparesis, neuropathy, leukoencephalopathy and gastrointestinal dysmotility leading to cachexia and early death. The reduction in TP activity results in reduced mtDNA synthesis, causing impaired mitochondrial function. Development of cell models would be helpful in the assessment of potential therapeutic options.
Aim: To determine whether olfactory cell lines derived from patients with MNGIE have reduced mitochondrial function.
Methods: We studied olfactory cell lines derived from patients with MNGIE. We performed FACS analysis to study the mitochondrial membrane potential (MMP), mitochondrial mass, apoptosis and cell death. ATP synthesis of cell lines were measured by a luciferin-luciferase based assay. DNA was extracted from cells and real-time quantitative PCR was performed to assess mtDNA copy number.
Results: MMP was reduced by 50% and mitochondrial mass was reduced to 26% in patient’s olfactory cell lines. There was no difference in the level of apoptosis or cell death between MNGIE and control cell cultures. The rate of ATP synthesis was reduced to 70 % (± 8.9) of control values. There was no difference in the ratio of mtDNA compared to nuclear DNA between patient and control DNA samples.
Conclusions: We detected reduced MMP, mitochondrial mass and ATP production in olfactory cell lines derived from patients with MNGIE syndrome. Olfactory cell lines may provide a cell model for the future assessment of pharmacological agents that are developed for the treatment of MNGIE syndrome.