The burden of heart failure (HF) in terms of health care expenditures, hospitalizations, and mortality is substantial and growing. The failing heart has been described as "energy-deprived" and mitochondrial dysfunction is a driving force associated with this energy supply-demand imbalance. Existing HF therapies provide symptomatic and longevity benefit by reducing cardiac workload through heart rate reduction and reduction of preload and afterload but do not address the underlying causes of abnormal myocardial energetic nor directly target mitochondrial abnormalities. Numerous studies in animal models of HF as well as myocardial tissue from explanted failed human hearts have shown that the failing heart manifests abnormalities of mitochondrial structure, dynamics, and function that lead to a marked increase in the formation of damaging reactive oxygen species and a marked reduction in on demand adenosine triphosphate synthesis. Correcting mitochondrial dysfunction therefore offers considerable potential as a new therapeutic approach to improve overall cardiac function, quality of life, and survival for patients with HF.
Keywords: ADP, adenosine diphosphate; ATP, adenosine triphosphate; CI (to V), complex I (to V); Drp, dynamin-related protein; ETC, electron transport chain; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular; MPTP, mitochondrial permeability transition pore; Mfn, mitofusin; OPA, optic atrophy; PGC, peroxisome proliferator-activated receptor coactivator; PINK, phosphatase and tensin homolog–inducible kinase; ROS, reactive oxygen species; TAZ, tafazzin; cardiolipin; heart failure; mitochondria; mtDNA, mitochondrial deoxyribonucleic acid; myocardial energetics; oxidative phosphorylation.
© 2020 The Author.