Perinuclear mitochondrial clustering for mesenchymal-to-epithelial transition in pluripotency induction

Abstract

<p>Remodeled mitochondria are characteristic of pluripotent stem cells. However, a role for mitochondrial movement and distribution in pluripotency remains unknown. Here, we show that mitochondrial retrograde transport-mediated perinuclear clustering via dynein complex occurs at the early phase of pluripotency induction. Interestingly, this mitochondrial redistribution is regulated by Yamanaka factor OCT4 but not SOX2 or KLF4. This mitochondrial redistribution, which has effect on the efficiency of somatic cell reprogramming, also depends on DRP1-mediated mitochondrial fission. Importantly, perinuclear mitochondrial clustering is required for mesenchymal-to-epithelial transition (MET), an early step in reprogramming, during which β-catenin regulates the MET process. Furthermore, sufficient amount of β-catenin plays a key role in maintaining stabilization of E-CADHERIN. Taken together, these studies show that perinuclear mitochondrial clustering is an essential organellar step for MET process of pluripotency induction, which may shed light on the subcellular relationship between mitochondrial dynamics, pluripotency, and cellular morphology.<br></p>