Inefficient coupling between proton transport and ATP synthesis may be the pathogenic mechanism for NARP and Leigh syndrome resulting from the T8993G mutation in mtDNA.

摘要: Mutations in the ATP6 gene of mtDNA (mitochondrial DNA) have been shown to cause several different neurological disorders. The product this is ATPase 6, an essential component F1F0-ATPase. In present study we show that function F1F0-ATPase impaired lymphocytes from ten individuals harbouring T8993G point mutation associated with NARP (neuropathy, ataxia and retinitis pigmentosa) Leigh syndrome. We both ATP synthase proton transport activity enzyme correlates amount mutated, ranging 13–94%. fluorescent dye RH-123 (Rhodamine-123) was used as a probe determine whether or not passive flux (i.e. intermembrane space matrix) affected by mutation. Under state 3 respiratory conditions, slight difference fluorescence quenching kinetics observed between mutant control mitochondria suggests marginally lower F0 capacity cells patients. Moreover, independent cellular load specific inhibitor oligomycin induced marked enhancement rate, which block conductivity through [Linnett Beechey (1979) Inhibitors synthethase system. Methods Enzymol. 55, 472–518]. Overall, results rule out previously proposed basis pathogenicity Since synthesis rate decreased 70% patients compared controls, suggest affects coupling translocation on F1. discuss our findings view current knowledge regarding rotary mechanism catalysis enzyme.