It is believed that mitochondrial dynamics is coordinated with endosomal traffic 
rates during cytoskeletal remodeling, but the mechanisms involved are largely 
unknown. The adenovirus early region 4 ORF4 protein (E4orf4) subverts signaling 
by Src family kinases (SFK) to perturb cellular morphology, membrane traffic, 
and organellar dynamics and to trigger cell death. Using E4orf4 as a model, we 
uncovered a functional connection between mitochondria-shaping proteins and the 
small GTPase Rab11a, a key regulator of polarized transport via recycling 
endosomes. We found that E4orf4 induced dramatic changes in the morphology of 
mitochondria along with their mobilization at the vicinity of a polarized actin 
network typifying E4orf4 action, in a manner controlled by SFK and Rab11a. 
Mitochondrial remodeling was associated with increased proximity between Rab11a 
and mitochondrial membranes, changes in fusion-fission dynamics, and 
mitochondrial relocalization of the fission factor dynamin-related protein 1 
(Drp1), which was regulated by the Rab11a effector protein FIP1/RCP. Knockdown 
of FIP1/RCP or inhibition of Drp1 markedly impaired mitochondrial remodeling and 
actin assembly, involving Rab11a-mediated mitochondrial dynamics in 
E4orf4-induced signaling. A similar mobilization of mitochondria near actin-rich 
structures was mediated by Rab11 and Drp1 in viral Src-transformed cells and 
contributed to the biogenesis of podosome rosettes. These findings suggest a 
role for Rab11a in the trafficking of Drp1 to mitochondria upon SFK activation 
and unravel a novel functional interplay between Rab11a and mitochondria during 
reshaping of the cell cytoskeleton, which would facilitate mitochondria 
redistribution near energy-requiring actin-rich structures.