Department of Physiology, Shantou University School of Medicine, Shantou, China.
Mol Cell Biol. 2014 May;34(10):1788-99. doi: 10.1128/MCB.00774-13. Epub 2014 Mar 10.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that mediate posttranscriptional gene silencing. Mitochondrial fission participates in the induction of apoptosis. It remains largely unknown whether miRNAs can regulate mitochondrial fission. Reactive oxygen species and doxorubicin could induce mitochondrial fission and apoptosis in cardiomyocytes. Concomitantly, mitofusin 1 (Mfn1) was downregulated, whereas miRNA 140 (miR-140) was upregulated upon apoptotic stimulation. We investigated whether Mfn1 and miR-140 play a functional role in mitochondrial fission and apoptosis. Ectopic expression of Mfn1 attenuated mitochondrial fission and apoptosis. Knockdown of miR-140 inhibited mitochondrial fission. Our results further revealed that knockdown of miR-140 was able to reduce myocardial infarct sizes in an animal model. We observed that miR-140 could suppress the expression of Mfn1, and it exerted its effect on mitochondrial fission and apoptosis through targeting Mfn1. Our data revealed that mitochondrial fission occurs in cardiomyocytes and can be counteracted by Mfn1. However, the function of Mfn1 is negatively regulated by miR-140. Our present work suggests that Mfn1 and miR-140 are integrated into the program of cardiomyocyte apoptosis.
微小 RNA（miRNA）是一类小的非编码 RNA，可介导转录后基因沉默。线粒体分裂参与细胞凋亡的诱导。miRNA 是否能调节线粒体分裂仍知之甚少。活性氧和阿霉素可诱导心肌细胞线粒体分裂和凋亡。同时，在凋亡刺激下，融合蛋白 1（Mfn1）下调，而 miRNA-140（miR-140）上调。我们研究了 Mfn1 和 miR-140 是否在线粒体分裂和凋亡中发挥功能作用。Mfn1 的异位表达减弱了线粒体分裂和凋亡。miR-140 的敲低抑制了线粒体分裂。我们的结果进一步表明，miR-140 的敲低能够减少动物模型中的心肌梗死面积。我们观察到 miR-140 可以抑制 Mfn1 的表达，它通过靶向 Mfn1 对线粒体分裂和凋亡发挥作用。我们的数据表明，线粒体分裂发生在心肌细胞中，可被 Mfn1 拮抗。然而，Mfn1 的功能受到 miR-140 的负调控。我们的研究表明，Mfn1 和 miR-140 整合到心肌细胞凋亡的程序中。
