Cytoskeleton-mitochondrion interactions during cellular stress

所有的细胞都配备了一个动态的细丝网络，称为细胞骨架。这种结构对于包括迁移、分裂和抵抗机械应力在内的各种重要功能是必不可少的。细胞脱水(所谓的高渗应激)与细胞萎缩有关，是细胞生存的主要威胁。我们以前的工作表明，细胞骨架在脱水、收缩的细胞中经历了强有力的重组，这一过程帮助细胞抵御随之而来的创伤。线粒体是一种双层膜包裹的细胞内细胞器，是细胞的动力源，是细胞生存和死亡的关键调节因子。有趣的是，这个细胞器也是动态的，表现出分裂和融合。我们发现细胞脱水和萎缩会导致线粒体的碎裂。此外，这一过程部分是通过细胞骨架的重塑来调节的。这意味着在细胞骨架和线粒体这两个主要的细胞系统之间存在结构和功能上的联系。这种交流可能对许多功能至关重要，包括运动、附着、抗应激、生存和程序性细胞死亡。然而，我们还不了解连接这些系统的生化和生物物理机制。我们的计划旨在弥合我们知识上的这一鸿沟。我们建议使用各种细胞和分子方法来了解细胞骨架和线粒体之间的关系。我们将研究在应力、细胞附着和运动的背景下，线粒体在细胞骨架重塑过程中是如何受到影响的。这些研究有可能深入了解基本的细胞机制，这些机制是正常和被破坏的细胞功能的基础，是适应或死亡的核心。

All cells are equipped with a dynamic meshwork of filaments, called the cytoskeleton. This structure is essential for a variety of vital functions including migration, division and resistance against mechanical stress. Cellular dehydration (so called hyperosmotic stress) is associated with cell shrinkage, and represents a major threat for cell survival. Our previous work has shown that the cytoskeleton undergoes robust reorganization in dehydrated, shrinking cells, and this process helps the cells withstand the ensuing trauma. The mitochondrion, a double membrane-enclosed intracellular organelle, is the power plant of the cells and a key regulator of cell survival and death. Interestingly, this organelle is also dynamic, exhibiting fission and fusion. We discovered that cellular dehydration and shrinkage results in the fragmentation of the mitochondrion. Moreover this process is partly mediated by the remodeling of the cytoskeleton. This means that there is a structural and functional communication between two major cellular systems: the cytoskeleton and the mitochondrion. Such communication may be critical for many functions including movement, attachment, stress resistance, survival and programmed cell death. However we do not yet understand the biochemical and biophysical mechanisms that link these systems. Our program aims to bridge this gap in our knowledge. We propose to use a variety of cellular and molecular approaches to understand the relationship between the cytoskeleton and the mitochondrion. We will investigate how the mitochondrion is affected during cytoskeleton remodeling in the context of stress, cell attachment and movement. These studies have the potential to generate insight into fundamental cellular mechanisms that underlie normal and disrupted cell functions, and are central to adaptation or death.