Dynamics of mitochondria promote stress granule fusion.

Abstract

As one of cellular responses against external stressors, stress granules are formed in the cytoplasm. It has been revealed that these granules are liquid-like, highly dynamic structures, widely believed to function as a transient storage for various cytoplasmic proteins and RNAs. While stress granule dynamics have been considered microtubule-dependent activities for a decade, current perspectives suggest that there is a close relationship between stress granules and membrane bound organelles in regards to dynamic properties of stress granules. This perspective has also been supported by several clinical findings that dysregulated dynamics of stress granules are hallmarks of several neurodegenerative diseases, which surprisingly coincides with dysfunctional mitochondria. However, regardless of accumulating evidence that there is a correlation between stress granules and mitochondria, very little is known about how stress granules and mitochondria are interconnected and why their functional relevance is critical for cell survival. Here, we found that stress granule dynamics are driven by mitochondrial dynamics. Mitochondria dependent stress granule mobility promotes stress granule fusion activities by which the presence of stress granules induces mitochondrial perinuclear clustering. Furthermore, mitochondria-mediated fusion activity may be newly defined as an essential pathway for cell survival by achieving proper recruitment of apoptotic factors into stress granules. We thus propose that mitochondrial dynamics plays a fundamental role in maintaining functional stress granules against stressful conditions.