Dynein-dependent positioning of multiple organelles regulates adaptive gene expression during oxidative stress

ABSTRACT Cells respond to environmental insults through well-characterized changes to their transcriptome and proteome. The contribution that reorganization of intracellular architecture makes to the adaptive stress response is much less understood. Here, we reveal a conserved spatial response to oxidative stress in which the microtubule motor dynein enhances perinuclear clustering of multiple membrane-bound organelles. These events are triggered by reactive oxygen species and protein kinase C and occur without increased association of dynein with its activator dynactin, pointing to a non-canonical mechanism for stimulating retrograde transport. Using a chemically-inducible system for dispersing individual organelles, we show that perinuclear localization of multiple compartments potentiates oxidative stress-induced gene expression, with distinct genes depending on inputs from either combinations of organelles or individual compartments. Together, these findings implicate positioning of multiple membrane-bound compartments in gene expression regulation and identify coordinated organelle trafficking by dynein as an additional regulatory layer in the cellular stress response.