Although mitochondrial fission has been reported to increase proliferative capacity and collagen production, it can also contribute to mitochondrial impairment, which is detrimental to cell survival. The aim of the present study was to investigate the role of mitochondrial fission in cardiac fibroblasts (CF) activation and explore the mechanisms involved in the maintenance of mitochondrial health under this condition. For this, changes in the levels of mitochondrial fission/fusion-related proteins were assessed in transforming growth factor beta 1 (TGF-β1)-activated CF, whereas the role of mitochondrial fission during this process was also elucidated, as were the underlying mechanisms. The interaction between mitochondrial fission and mitophagy, the main defense mechanism against mitochondrial impairment, was also explored. The results showed that the mitochondria in TGF-β1-treated CF were noticeably more fragmented than those of controls. The expression of several mitochondrial fission-related proteins was markedly upregulated, and the levels of fusion-related proteins were also altered, but to a lesser extent. Inhibiting mitochondrial fission resulted in a marked attenuation of TGF-β1-induced CF activation. The TGF-β1-induced increase in glycolysis was greatly suppressed in the presence of a mitochondrial inhibitor, whereas a glycolysis-specific antagonist exerted little additional antifibrotic effects. TGF-β1 treatment increased cellular levels of reactive oxygen species (ROS) and triggered mitophagy, but this effect was reversed following the application of ROS scavengers. For the signals mediating mitophagy, the expression of Pink1, but not Bnip3l/Nix or Fundc1, exhibited the most significant changes, which could be counteracted by treatment with a mitochondrial fission inhibitor. Pink1 knockdown suppressed CF activation and mitochondrial fission, which was accompanied by increased CF apoptosis. In conclusion, mitochondrial fission resulted in increased glycolysis and played a crucial role in CF activation. Moreover, mitochondrial fission promoted reactive oxygen species (ROS) production, leading to mitophagy and the consequent degradation of the impaired mitochondria, thus promoting CF survival and maintaining their activation.

尽管据报道线粒体裂变可以增加增殖能力和胶原蛋白的产生，但它也可能导致线粒体损伤，这对细胞存活是有害的。本研究的目的是研究线粒体裂变在心脏成纤维细胞 (CF) 激活中的作用，并探讨在这种情况下维持线粒体健康的机制。为此，在转化生长因子 β 1 (TGF-β1) 激活的 CF 中评估了线粒体裂变/融合相关蛋白水平的变化，而线粒体裂变在此过程中的作用以及潜在机制也得到了阐明. 还探讨了线粒体裂变和线粒体自噬之间的相互作用，这是针对线粒体损伤的主要防御机制。结果表明，TGF-β1 处理的 CF 中的线粒体明显比对照中的线粒体更加碎片化。几种线粒体裂变相关蛋白的表达显着上调，融合相关蛋白的水平也发生了变化，但程度较轻。抑制线粒体裂变导致 TGF-β1 诱导的 CF 活化显着减弱。在线粒体抑制剂存在下，TGF-β1 诱导的糖酵解增加被大大抑制，而糖酵解特异性拮抗剂几乎没有额外的抗纤维化作用。TGF-β1 处理增加了活性氧 (ROS) 的细胞水平并触发了线粒体自噬，但在应用 ROS 清除剂后，这种作用被逆转。对于介导线粒体自噬的信号，Pink1 的表达，但不是 Bnip3l/Nix 或 Fundc1，表现出最显着的变化，这可以通过用线粒体裂变抑制剂治疗来抵消。Pink1 敲低抑制了 CF 活化和线粒体裂变，伴随着 CF 细胞凋亡增加。总之，线粒体裂变导致糖酵解增加，并在 CF 激活中起关键作用。此外，线粒体裂变促进了活性氧 (ROS) 的产生，导致线粒体自噬和受损线粒体的降解，从而促进 CF 存活并维持其活化。线粒体裂变导致糖酵解增加，并在 CF 活化中起关键作用。此外，线粒体裂变促进了活性氧 (ROS) 的产生，导致线粒体自噬和受损线粒体的降解，从而促进 CF 存活并维持其活化。线粒体裂变导致糖酵解增加，并在 CF 活化中起关键作用。此外，线粒体裂变促进了活性氧 (ROS) 的产生，导致线粒体自噬和受损线粒体的降解，从而促进 CF 存活并维持其活化。