Mitochondrial Remodeling During Hyperosmotic Stress

• Main Author: Zulys, Matthew
• Other Authors: Kapus, Andras
• Format: Others
• Language: en_ca
• Published: 2008
• Subjects: Hyperosmotic stress; mitochondria; 0307
• Online Access: http://hdl.handle.net/1807/17240

Hyperosmotic stress represents a major threat to cellular integrity and may lead to cell death via apoptosis. Accordingly, each cell reacts to hyperosmolarity with a set of functional and structural compensatory responses. Recently it has been shown that the mitochondria remodel during hyperosmotic stress. Although changes in mitochondrial dynamics could be crucial for both adaptation and apoptosis, hyperosmolarity-induced mitochondrial remodeling has not been characterized. We found that hyperosmotic stress translocates dynamin like protein 1 (DLP-1) to the mitochondria and induces DLP-1 mediated, F-actin-modulated, Rac-dependent fragmentation of these organelles in LLC-PK1 cells. Downregulation of DLP-1 mitigates the activation of the osmotic response element and increases the susceptibility of tubular cells to hyperosmotically-induced apoptosis, suggesting that DLP-1 (or mitochondrial fragmentation) may have a protective role during osmotic stress. The hyperosmolarity-triggered remodeling of the mitochondrion represents a hitherto unrecognized response to osmotic shock, which may have significant impact on adaptation and apoptosis.