Mitochondria-derived vesicles serve as reactors in response to stress in cardiomyocytes.

BACKGROUND: Mitochondria-derived vesicles (MDVs) are a novel type of mitochondrial quality control (MQC) found in different types of cells. Strictly-organized adult cardiomyocytes contain abundant mitochondria; however, the precise characteristics and functions of MDVs in the heart remain unclear. METHODS: Rat cardiomyocytes were examined using transmission electron microscopy (TEM) to visualize MDVs. Live-cell imaging with STED microscopy and fluorescent mitochondrial dyes (PK Mito Red and PK Mito Deep Red) was performed to track MDV dynamics in neonatal and adult rat cardiomyocytes. Nanoparticle tracking analysis (NTA) was used to assess the size and quantity of MDVs. MDVs were purified from heart mitochondria, and their protein profile was analyzed by proteomics. RNA sequencing was conducted on neonatal cardiomyocytes treated with MDVs to explore transcriptomic changes. RESULTS: MDVs were observed in live rat cardiomyocytes with TEM revealing vesicles 70-150 nm in diameter. MDVs were universally distributed, showed active motility, and colocalized with other intracellular organelles in adult cardiomyocytes. Proteomics analysis showed MDV-associated proteins and found that the respiratory functions of MDVs were preserved in cardiomyocytes. The number of MDVs in cardiomyocytes was found to increase in response to various acute physiological and pathological stimuli. By increasing the number of MDVs in cardiomyocytes with exogenously purified myocardial MDVs and analyzing transcriptomic changes via RNA sequencing, we found that a greater number of MDVs in cardiomyocytes altered genes in stress-related signaling pathways. CONCLUSION: MDVs in cardiomyocytes colocalize with other organelles, which might facilitate inter-organelle communication, and serve as reactors in response to stress in adult cardiomyocytes.