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Abstract
Mitochondria, the dynamic energy powerhouses of the cell, have vital roles in a multitude of cellular processes including differentiation and cell survival. Tight regulation of mitochondrial dynamics, integrity, and function is indispensible for preservation of homeostasis in all cells, including pluripotent stem cells. The ability to proliferate and self-renew indefinitely bestows the pluripotent embryonic stem cells (ESCs) with immense curative potential. Mechanisms that preserve mitochondrial well-being, and therefore maintain "stemness", are vital in realizing the full potential of ESCs in therapeutic regenerative medicine. However, virtually nothing is known regarding the regulation of mitochondrial dynamics and function and the relationship thereof to overall cell fate and function in pluripotent ESCs or other somatic stem cells. Using loss- and gain-of-function approaches, we show that growth factor erv1-like (Gfer) plays an essential pro-survival role in the maintenance of murine ESC pluripotency by preserving the structural and functional integrity of their mitochondria, through modulation of the key mitochondrial fission factor Drp1.