Primary disorders of mitochondrial ATP synthase belong to the most severe mitochondrial diseases. They can be caused by heteroplasmic mtDNA mutations in ATP6 gene that affect ability of enzyme to synthesise ATP, or by mutations in nuclear genes encoding factors essential for biosynthesis and assembly of the catalytic F1-part of the enzyme. In the latter case the cellular content of the enzyme decreases to ≤30 %. In both types of defects low production of ATP appears to be associated with increased mitochondrial ROS production related to elevated levels of mitochondrial membrane potential.

        Key words: Mitochondrial diseases, cardiomyopathy, ATP synthase, oxidative phosphorylation, respiratory chain complexes.