During cancer cell invasion, faster moving cancer cells play a dominant role by 
invading further and metastasizing earlier. Despite the importance of these 
outlier cells, the source of heterogeneity in their migratory behavior remains 
poorly understood. Here, we show that anterior localization of mitochondria, in 
between the nucleus and the leading edge of migrating epithelial cancer cells, 
correlates with faster migration velocities and increased directional 
persistence. The asymmetry of mitochondrial localization along the axis of 
migration is absent during spontaneous cell migration on two-dimensional 
surfaces and only occurs in the presence of chemical attractant cues or in 
conditions of mechanical confinement. Moreover, perturbing the asymmetric 
distribution of mitochondria within migrating cells by interfering with 
mitochondrial fusion (opa-1) or fission (drp-1) proteins, significantly reduces 
the number of cells with anterior localization of mitochondria and significantly 
decreases the velocity and directional persistence of the fastest moving cells. 
We also observed similar changes after perturbing the linkage between 
mitochondria and microtubules by the knockdown of mitochondrial rhoGTPase-1 
(miro-1). Taken together, the changes in migration velocity and directional 
persistence in cells with anterior-localized mitochondria could account for an 
order of magnitude differences in invasive abilities between cells from 
otherwise homogenous cell populations.