Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Nat Commun. 2024 May 7;15(1):3793. doi: 10.1038/s41467-024-48189-1.
Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.
在细胞周期中，线粒体动力学受肌动蛋白聚合/解聚的循环波调节。在中期，该波在线粒体上诱导肌动蛋白彗星尾巴，推动这些细胞器进行空间混合，从而使它们在子细胞中均等遗传。相比之下，在间期，循环肌动蛋白波促进局部线粒体裂变。在这里，我们确定 F-肌动蛋白成核蛋白/延伸因子 FMNL1 是波的正调节剂。FMNL1 耗尽的细胞表现出线粒体极化减少、线粒体耗氧量减少和活性氧产生增加。伴随这些变化的是波片段化线粒体异质融合的丧失。因此，我们提出，间期肌动蛋白波通过促进线粒体内容混合来维持线粒体的动态平衡。最后，我们研究了观察到的波在中期驱动线粒体运动而在间期驱动线粒体裂变的机制基础。我们的数据表明，当肌动蛋白聚合的力受到线粒体与微管的束缚时，就像在间期一样，会导致裂变。
