@article {Pernaute835751, author = {Barbara Pernaute and Juan Miguel S{\'a}nchez Nieto and Salvador P{\'e}rez-Montero and Aida di Gregorio and Ana Lima and Katerina Lawlor and Sarah Bowling and Gianmaria Liccardi and Alejandra Tom{\'a}s and Pascal Meier and Guy A. Rutter and Ivana Barbaric and Tristan A. Rodr{\'\i}guez}, title = {DRP1-mediated regulation of mitochondrial dynamics determines the apoptotic response upon embryonic differentiation}, elocation-id = {835751}, year = {2019}, doi = {10.1101/835751}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The changes that drive differentiation create a large potential for the emergence of abnormal cells that need to be removed before they contribute to further development or the germline. This removal is in part achieved by cells becoming hypersensitive to death upon exit of na{\"\i}ve pluripotency. What causes this change in apoptotic response is unknown. Here we identify that it is controlled by the regulator of mitochondrial dynamics DRP1. We show that in mouse, na{\"\i}ve pluripotent cells have fragmented mitochondria due to high DRP1-mediated fission, but upon differentiation, DRP1 activity decreases, inducing mitochondria to fuse and form complex networks. We demonstrate that this decrease in DRP1 activity lowers the apoptotic threshold, as mutation of DRP1 increases the sensitivity to cell death and its over-expression protects against apoptosis. Together, our findings highlight how regulation of mitochondrial dynamics allows cells to adapt their apoptotic response to the changing environment of differentiation.}, URL = {https://www.biorxiv.org/content/early/2019/11/08/835751}, eprint = {https://www.biorxiv.org/content/early/2019/11/08/835751.full.pdf}, journal = {bioRxiv} }