The therapeutic potential of targeting ferroptosis in the treatment of mitochondrial cardiomyopathies and heart failure

Ferroptosis is a form of iron-regulated cell death implicated in a wide array of diseases, including heart failure, hypertension, and numerous cardiomyopathies. Additionally, mitochondrial dysfunction has been associated with several of these same disease states. However, the role of the mitochondrion in ferroptotic cell death remains debated. As a major regulator of cellular iron levels, the mitochondria may very well play a crucial role in the mechanisms behind ferroptosis, but at this point, this has not been adequately defined. Emerging evidence indicates a critical role of mitochondrial Sirtuin 3 (SIRT3), a deacetylase linked with longevity and protection against numerous conditions, in the prevention of cardiovascular diseases. Here, the authors provide a brief overview of the potential roles of SIRT3 in mitochondrial iron homeostasis, as well as its contribution to the mitochondrial cardiomyopathy of Friedreich's ataxia (FRDA) and diabetic cardiomyopathy (DCM). The authors also discuss the current knowledge of the involvement of ferroptosis and the mitochondria in these and other cardiovascular disease states, including doxorubicin-induced cardiomyopathy, and provide insight into areas requiring further investigation.

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