Abstract
Myocardial ischemia reduces the supply of oxygen and nutrients to cardiomyocytes, leading to an energetic crisis or cell death. Mitochondrial dysfunction is a decisive contributor to the reception, transmission, and modification of cardiac ischemic signals. Cells with damaged mitochondria exhibit impaired mitochondrial metabolism and increased vulnerability to death stimuli due to disrupted mitochondrial respiration, reactive oxygen species overproduction, mitochondrial calcium overload, and mitochondrial genomic damage. Various intracellular and extracellular stress signaling pathways converge on mitochondria, so dysfunctional mitochondria tend to convert from energetic hubs to apoptotic centers. To interrupt the stress signal transduction resulting from lethal mitochondrial damage, cells can activate mitophagy (mitochondria-specific autophagy), which selectively eliminates dysfunctional mitochondria to preserve mitochondrial quality control. Different pharmacological and non-pharmacological strategies have been designed to augment the protective properties of mitophagy and have been validated in basic animal experiments and pre-clinical human trials. In this review, we describe the process of mitophagy in cardiomyocytes under ischemic stress, along with its regulatory mechanisms and downstream effects. Then, we discuss promising therapeutic approaches to preserve mitochondrial homeostasis and protect the myocardium against ischemic damage by inducing mitophagy.
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This work was supported by grants from the Heilongjiang Natural Science Foundation Joint Guidance Project of China (No. LH2019H115).
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Tong Fu and Yanchun Ma contributed to article collection and data analysis. Yan Li and Yingwei Wang contributed to figure preparation and table organization. Qi Wang and Ying Tong wrote the draft. All the authors approved this submission.
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Fu, T., Ma, Y., Li, Y. et al. Mitophagy as a mitochondrial quality control mechanism in myocardial ischemic stress: from bench to bedside. Cell Stress and Chaperones 28, 239–251 (2023). https://doi.org/10.1007/s12192-023-01346-9
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DOI: https://doi.org/10.1007/s12192-023-01346-9