Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA.
Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA
J Cell Sci. 2021 Feb 8;134(3):jcs248385. doi: 10.1242/jcs.248385.
Attention has long focused on the actin cytoskeleton as a unit capable of organizing into ensembles that control cell shape, polarity, migration and the establishment of intercellular contacts that support tissue architecture. However, these investigations do not consider observations made over 40 years ago that the actin cytoskeleton directly binds metabolic enzymes, or emerging evidence suggesting that the rearrangement and assembly of the actin cytoskeleton is a major energetic drain. This Review examines recent studies probing how cells adjust their metabolism to provide the energy necessary for cytoskeletal remodeling that occurs during cell migration, epithelial to mesenchymal transitions, and the cellular response to external forces. These studies have revealed that mechanotransduction, cell migration, and epithelial to mesenchymal transitions are accompanied by alterations in glycolysis and oxidative phosphorylation. These metabolic changes provide energy to support the actin cytoskeletal rearrangements necessary to allow cells to assemble the branched actin networks required for cell movement and epithelial to mesenchymal transitions and the large actin bundles necessary for cells to withstand forces. In this Review, we discuss the emerging evidence suggesting that the regulation of these events is highly complex with metabolism affecting the actin cytoskeleton and vice versa.
长期以来，人们一直关注肌动蛋白细胞骨架作为一个能够组织成集合体的单位，这些集合体控制着细胞的形状、极性、迁移以及建立支持组织架构的细胞间接触。然而，这些研究并没有考虑到 40 多年前观察到的肌动蛋白细胞骨架直接结合代谢酶的现象，也没有考虑到新兴的证据表明肌动蛋白细胞骨架的重排和组装是能量的主要消耗。这篇综述探讨了最近的研究，这些研究探讨了细胞如何调整其代谢，为细胞迁移、上皮细胞向间充质转化以及细胞对外力的反应过程中发生的细胞骨架重塑提供必要的能量。这些研究表明，机械转导、细胞迁移和上皮细胞向间充质转化伴随着糖酵解和氧化磷酸化的改变。这些代谢变化提供能量，支持肌动蛋白细胞骨架的重排，使细胞能够组装分支的肌动蛋白网络，从而进行细胞运动和上皮细胞向间充质转化，以及组装抵抗外力所需的大的肌动蛋白束。在这篇综述中，我们讨论了新兴的证据，表明这些事件的调节非常复杂，代谢影响肌动蛋白细胞骨架，反之亦然。
