Elamipretide Improves Mitochondrial Function in the Failing Human Heart

• Mitochondrial function is impaired in explanted failing pediatric and adult human hearts. • Elamipretide is a novel mitochondria-targeted drug that is targeted to cardiolipin on the inner mitochondrial membrane and improves coupling of the electron transport chain. • Treatment of explanted human hearts with elamipretide improves human cardiac mitochondrial function. • The study provides novel methods to evaluate the influence of compounds on mitochondria in the human heart and provides proof of principle for the use of elamipretide to improve mitochondrial energetics in failing myocardium due to multiple etiologies and irrespective of age. Negative alterations of mitochondria are known to occur in heart failure (HF). This study investigated the novel mitochondrial-targeted therapeutic agent elamipretide on mitochondrial and supercomplex function in failing human hearts ex vivo. Freshly explanted failing and nonfailing ventricular tissue from children and adults was treated with elamipretide. Mitochondrial oxygen flux, complex (C) I and CIV activities, and in-gel activity of supercomplex assembly were measured. Mitochondrial function was impaired in the failing human heart, and mitochondrial oxygen flux, CI and CIV activities, and supercomplex-associated CIV activity significantly improved in response to elamipretide treatment. Elamipretide significantly improved failing human mitochondrial function.