Mitochondria-Coupled Hitchhiking Drives Vimentin Intermediate Filament Transport

Vimentin intermediate filaments (VIFs) undergo active microtubule-dependent transport throughout the cell, with trajectories resembling those of motor-driven organelles, yet our recent work showed that only a small subset of VIFs lies close to microtubules. How VIFs engage the microtubule-based transport machinery, and whether additional transport routes contribute, remain unresolved. We hypothesized that VIFs move indirectly, by hitchhiking on motile organelles, and tested this using mitochondria. Live imaging showed mitochondria and adjacent VIFs moving together, and volume electron microscopy revealed VIFs closely following mitochondrial surfaces at sites distinct from microtubule contacts. Depleting the mitochondrial motor adaptor TRAK1 to inhibit anterograde mitochondrial transport shifted both mitochondria and VIFs toward the nucleus. Driving mitochondria toward the cell periphery with a tailless kinesin-1 in cells lacking endogenous kinesin-1, or toward the cell center with a minus-end-directed motor, redistributed a subset of VIFs in the same direction. Thus, VIF transport to a large extend is accomplished by hitchhiking on motile mitochondria.