Abstract
Mitochondria are dynamic organelles that alter their morphology through fission (fragmentation) and fusion (elongation). These morphological changes correlate highly with mitochondrial functional adaptations to stressors, such as hypoxia, pressure overload, and inflammation, and are important in the setting of heart failure. Pathological mitochondrial remodeling, characterized by increased fission and reduced fusion, is associated with impaired mitochondrial respiration, increased mitochondrial oxidative stress, abnormal cytoplasmic calcium handling, and increased cardiomyocyte apoptosis. Considering the impact of the mitochondrial morphology on mitochondrial behavior and cardiomyocyte performance, altered mitochondrial dynamics could be expected to induce or exacerbate the pathogenesis and progression of heart failure. However, whether alterations in mitochondrial fission and fusion accelerate or retard the progression of heart failure has been the subject of intense debate. In this review, we first describe the physiological processes and regulatory mechanisms of mitochondrial fission and fusion. Then, we extensively discuss the pathological contributions of mitochondrial fission and fusion to heart failure. Lastly, we examine potential therapeutic approaches targeting mitochondrial fission/fusion to treat patients with heart failure.
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This study is supported by the Key R&D Program of the People’s Republic of China (2019YFC1711700).
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Xinxin Liu contributed to the review writing, Chenchen Guo contributed to the article collection, and Qiming Zhang contributed to the manuscript revision. All the authors approved this submission.
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Liu, X., Guo, C. & Zhang, Q. Novel insights into the involvement of mitochondrial fission/fusion in heart failure: From molecular mechanisms to targeted therapies. Cell Stress and Chaperones 28, 133–144 (2023). https://doi.org/10.1007/s12192-023-01321-4
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DOI: https://doi.org/10.1007/s12192-023-01321-4