Cell Migration is Regulated by Mitochondria and Endoplasmic Reticulum Morphology.

Abstract

Cell migration is essential for homeostasis and the development of metastases. We hypothesize that cell migration is regulated by mitochondria and endoplasmic reticulum morphology. Using live cell microscopy, we found that mitochondria specifically migrate into the biochemically dense leading edge of the cell interacting with focal adhesions as well. At the leading edge the mitochondria are visibly shorter and less tubular than the perinuclear area. This is related to the elevated levels of fission events per minute in the leading edge and elevated levels of fusion events per minute in the trailing edge. We observe that mitochondria migrate along microtubules and simultaneously interact with the ER. When the ER is sheet-like the mitochondria are longer and tubular and when the ER is tubular the mitochondria are shorter and punctate. This change in ER and mitochondria morphology changes the cell’s ability to migrate. CLIMP63 cells have more sporadic turns, take longer to make turns, have shorter distances travelled and shorter displacements. To determine whether mitochondria dynamics play a role we examined these cell migration parameters in the presence of OPA1 and Drp1. This allowed us to conclude that the ER morphology is responsible for the distance and displacement the cell travels while the mitochondria is responsible for the angles the cell turns. When the ER is sheet-like the cells will be travel shorter total distances and displacements and when the cell has longer mitochondria it will be sporadic turns and take longer to make these turns.