Nicotinamide nucleotide transhydrogenase and bioenergetic metabolism in complex I defective cardiac mitochondria

At least one in 5000 individuals are born with inherited mitochondrial diseases from which 30- 40% are complex I defects that lead to cardiomyopathy, heart failure and death. A large proportion of chronic conditions (diabetes, coronary artery disease, heart failure, aging) develop mitochondrial complex I defects that are key factors promoting disease progression and cardiac complications. Either inherited or acquired, mitochondrial complex I defects have no cure. We propose that the mitochondrial enzyme, nicotinamide nucleotide transhydrogenase, is a novel therapeutic target that preserves cardiac oxidative metabolism and function and alleviates mitochondrial cardiomyopathies.