Mitochondrial quality control (MQC) is an adaptive response that adjusts the morphology and function of mitochondria during cardiovascular disorders. After exposure to stress, cardiomyocytes employ antioxidative factors to neutralize mitochondrial ROS, reduce oxidative stress damage, and ensure mitochondrial homeostasis. Concurrently, mitochondrial fission is activated so that damaged mitochondrial fractions can be removed from the mitochondrial network, with the cooperation of mitophagy. In contrast, healthy, long mitochondria can integrate with several small mitochondrial fragments to enhance the resistance of the entire mitochondrial population to stress. When these adaptive responses fail, programmed cell death by apoptosis or necroptosis is activated, and damaged mitochondria become the inducers of cell death, enabling the sequestration of incurable and dysfunctional cardiomyocytes.

During this process, mitochondrial fission and mitophagy serve as a double-edged sword in the damaged heart: on the one hand, they exert prosurvival mechanisms by isolating damaged mitochondria, and on the other hand, if fission and mitophagy persist beyond a certain threshold, they may lead to cellular demise. Therefore, selective, effective, moderate, and differential activation of mitophagy and mitigation of fission are essential for MQC and could synergistically sustain cardiac function. Necroptosis and apoptosis, although activated by various stimuli, are functionally governed solely by mitochondria. As the final steps of MQC to maintain tissue homeostasis, necroptosis and apoptosis communicate with each other and offer new targets for therapeutic approaches. Therefore, defects in MQC may determine the fate of cardiomyocytes.

The aim of this Special Issue is to collate original research and review articles that discuss the regulatory mechanisms and pathological effects of MQC in cardiovascular diseases, highlighting potential targets for the clinical management of acute and chronic myocardial injuries.

Potential topics include but are not limited to the following:

• New insights into the mechanisms underlying dysregulated mitochondrial quality control in the pathogenesis of myocardial and microvascular injuries
• The roles of oxidative stress, mitochondrial fission, mitochondrial fusion, mitochondrial biogenesis, mitophagy, mitochondria-induced death, and mitochondrial unfolded protein response in cardiovascular disorders
• Mitochondria-targeted approaches (such as melatonin or mitochondria-derived peptides) to attenuate the vulnerability of cardiomyocytes and endothelial cells to stressful conditions including oxidative stress, hypoxia, inflammation, ischemia-reperfusion injury, hyperglycemia, and lipotoxicity
• Clinically relevant information on the effects of therapies for myocardium and microvessels with a focus on mitochondria
• Novel approaches to modulate mitochondrial integrity and thus improve cardiovascular function during stressful conditions