Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mouse embryo fibroblasts lacking S6K1 (S6K1-KO MEFs) exhibited more fragmented mitochondria and a higher level of Dynamin related protein 1 (Drp1) and active Drp1 (pS616) in both whole cell extracts and mitochondrial fraction. In addition, there was no evidence for autophagy and mitophagy induction in S6K1 depleted cells. Glycolysis and mitochondrial respiratory activity was higher in S6K1-KO MEFs, whereas OxPhos ATP production was not altered. However, inhibition of Drp1 by Mdivi1 (Drp1 inhibitor) resulted in higher OxPhos ATP production and lower mitochondrial membrane potential. Taken together the depletion of S6K1 increased Drp1-mediated fission, leading to the enhancement of glycolysis. The fission form of mitochondria resulted in lower yield for OxPhos ATP production as well as in higher mitochondrial membrane potential. Thus, these results have suggested a potential role of S6K1 in energy metabolism by modulating mitochondrial respiratory capacity and mitochondrial morphology.

线粒体形态与新陈代谢，细胞周期，细胞发育和细胞死亡的变化有关，受到融合与裂变之间的平衡的严格控制。在这项研究中，我们发现S6激酶1（S6K1）有助于线粒体动力学，体内稳态和功能。缺少S6K1（S6K1-KO MEF）的小鼠胚胎成纤维细胞在全细胞提取物和线粒体部分均显示出更多的线粒体碎片和更高的Dynamin相关蛋白1（Drp1）和活性Drp1（pS616）水平。此外，在S6K1耗尽的细胞中没有自噬和线粒体诱导的证据。S6K1-KO MEFs的糖酵解和线粒体呼吸活性更高，而OxPhos ATP的产量没有改变。然而，Mdivi1（Drp1抑制剂）对Drp1的抑制作用导致OxPhos ATP产生更高，线粒体膜电位更低。总而言之，S6K1的耗竭增加了Drp1介导的裂变，导致糖酵解的增强。线粒体的裂变形式导致OxPhos ATP生产的产量降低，并且线粒体膜电位更高。因此，这些结果表明通过调节线粒体呼吸能力和线粒体形态，S6K1在能量代谢中具有潜在作用。