Mitochondrial membrane transporters and metabolic switch in heart failure

Mitochondrial dysfunction is widely recognized as a major factor for the progression of cardiac failure. Mitochondrial uptake of metabolic substrates and their utilization for ATP synthesis, electron transport chain activity, reactive oxygen species levels, ion homeostasis, mitochondrial biogenesis, and dynamics as well as levels of reactive oxygen species in the mitochondria are key factors which regulate mitochondrial function in the normal heart. Alterations in these functions contribute to adverse outcomes in heart failure. Iron imbalance and oxidative stress are also major factors for the evolution of cardiac hypertrophy, heart failure, and aging-associated pathological changes in the heart. Mitochondrial ATP–binding cassette (ABC) transporters have a key role in regulating iron metabolism and maintenance of redox status in cells. Deficiency of mitochondrial ABC transporters is associated with an impaired mitochondrial electron transport chain complex activity, iron overload, and increased levels of reactive oxygen species, all of which can result in mitochondrial dysfunction. In this review, we discuss the role of mitochondrial ABC transporters in mitochondrial metabolism and metabolic switch, alterations in the functioning of ABC transporters in heart failure, and mitochondrial ABC transporters as possible targets for therapeutic intervention in cardiac failure.