RT Journal Article SR Electronic T1 DRP1-mediated regulation of mitochondrial dynamics determines the apoptotic response upon embryonic differentiation JF bioRxiv FD Cold Spring Harbor Laboratory SP 835751 DO 10.1101/835751 A1 Barbara Pernaute A1 Juan Miguel Sánchez Nieto A1 Salvador Pérez-Montero A1 Aida di Gregorio A1 Ana Lima A1 Katerina Lawlor A1 Sarah Bowling A1 Gianmaria Liccardi A1 Alejandra Tomás A1 Pascal Meier A1 Guy A. Rutter A1 Ivana Barbaric A1 Tristan A. Rodríguez YR 2019 UL http://biorxiv.org/content/early/2019/11/08/835751.abstract AB 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 naïve 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, naïve 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.