Cytoskeleton-mitochondrion interactions during cellular stress

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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.