Preserving mitochondria to treat hypertrophic cardiomyopathy: From rare mitochondrial DNA mutation to heart failure therapy?

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  Figure 1. Restoration of mitochondrial structure and function ameliorates pathologic cardiac hypertrophy and preserves normal function. (A) Mitochondria in cardiac cells support high energy demands for the function of a healthy heart. (B) Mutations in mitochondrial DNA can provoke mitochondrial fragmentation with loss of cristae and trigger hypertrophic cardiomyopathy. Treatment with DNJ restores mitochondrial structure with normalization of cristae, despite presence of the mitochondrial DNA mutation, to prevent cardiac myocyte hypertrophy. It remains unknown whether treatment with DNJ will prevent development of hypertrophic cardiomyopathy or reverse established disease. Whether DNJ stimulates mitophagy to restore normal mitochondria also remains to be determined. (C) Prohypertrophic stimuli, such as hemodynamic overload, can also result in loss of mitochondrial function, independent of mutations in mitochondrial DNA, and result in pathologic cardiac hypertrophy and cardiomyopathic decompensation. Treatment of mice with angiotensin II as a model to mimic the effects of hemodynamic overload induces mitochondrial structural and functional defects, including mitochondrial fragmentation with…