Measurement of ATP production in mitochondrial disorders

Summary Mitochondrial diseases are a heterogeneous group of disorders caused by mutations in both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Mitochondrial disease leads to impaired respiratory chain function and reduced ATP production. The aim of this study was to compare disturbances in mitochondrial function by measuring ATP synthesis in fibroblasts derived from patients with nDNA and mtDNA defects. Skin fibroblasts derived from 22 patients with either nDNA‐related disorders (n = 8) or mtDNA‐related disorders (n = 14) were analysed. ATP synthesis was markedly decreased in fibroblasts derived from patients with nDNA‐related disorders but only variably so in patients with mtDNA mutations. In fibroblasts with the MELAS 3243A > G mutation, ATP synthesis correlated with mutant load. We believe that the observed differences in ATP production between cell lines derived from patients with nDNA‐related disorders and mtDNA‐related disorders may help in the assessment of patients with undiagnosed mitochondrial disease. The clinical comparisons observed in patients with nDNA‐ and mtDNA‐related disorders may be explained by differences in the disturbance of ATP synthesis measured in the two conditions.