MTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells

• DOI: 10.1038/s41467-018-07519-w
• Publication Date: 2018-11-27T15:37:56Z
• Authors: Amir Bahat; Andres Goldman; Yehudit Zaltsman; Dilshad H. Khan; Coral Halperin; Emmanuel Amzallag; Vladislav Krupalnik; Michael Mullokandov; Alon Silberman; Ayelet Erez; Aaron D. Schimmer; Jacob H. Hanna; Atan Gross
• Keywords: Dynamins; Mice, Knockout; Pluripotent Stem Cells; 0301 basic medicine; 0303 health sciences; Microscopy, Confocal; Science; Q; Gene Expression; Mouse Embryonic Stem Cells; Nanog Homeobox Protein; Mitochondrial Dynamics; Mitochondrial Membrane Transport Proteins; Article; GTP Phosphohydrolases; Mitochondria; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 13. Climate action; Animals; Cells, Cultured

Abstract The role of mitochondria dynamics and its molecular regulators remains largely unknown during naïve-to-primed pluripotent cell interconversion. Here we report that mitochondrial MTCH2 is a regulator fusion, essential for the interconversion murine embryonic stem cells (ESCs). During this interconversion, wild-type ESCs elongate their slightly alter glutamine utilization. In contrast, −/− fail to metabolism, maintaining high levels histone acetylation expression naïve pluripotency markers. Importantly, enforced elongation by pro-fusion protein Mitofusin (MFN) 2 or dominant negative form pro-fission dynamin-related (DRP) 1 sufficient drive exit from both ESCs. Taken together, our data indicate elongation, governed MTCH2, plays critical constitutes an early driving force in