Mitochondrial Ca(2+) uptake controls actin cytoskeleton dynamics during cell migration.

TitleMitochondrial Ca(2+) uptake controls actin cytoskeleton dynamics during cell migration.
Publication TypeJournal Article
Year of Publication2016
AuthorsPrudent, J, Popgeorgiev, N, Gadet, R, Deygas, M, Rimokh, R, Gillet, G
JournalSci Rep
Volume6
Pagination36570
Date Published2016 Nov 09
ISSN2045-2322
Abstract

Intracellular Ca(2+) signaling regulates cell migration by acting on cytoskeleton architecture, cell directionality and focal adhesions dynamics. In migrating cells, cytosolic Ca(2+) pool and Ca(2+) pulses are described as key components of these effects. Whereas the role of the mitochondrial calcium homeostasis and the Mitochondria Cacium Uniporter (MCU) in cell migration were recently highlighted in vivo using the zebrafish model, their implication in actin cystokeleton dynamics and cell migration in mammals is not totally characterized. Here, we show that mcu silencing in two human cell lines compromises their migration capacities. This phenotype is characterized by actin cytoskeleton stiffness, a cell polarization loss and an impairment of the focal adhesion proteins dynamics. At the molecular level, these effects appear to be mediated by the reduction of the ER and cytosolic Ca(2+) pools, which leads to a decrease in Rho-GTPases, RhoA and Rac1, and Ca(2+)-dependent Calpain activites, but seem to be independent of intracellular ATP levels. Together, this study highlights the fundamental and evolutionary conserved role of the mitochondrial Ca(2+) homeostasis in cytoskeleton dynamics and cell migration.

DOI10.1038/srep36570
Alternate JournalSci Rep
Citation Key10.1038/srep36570
PubMed ID27827394
PubMed Central IDPMC5101530