A new role of iridium(III) complexes in regulating pluripotency acquisition via mitochondrial remodulation

Induced pluripotent stem cells (iPSCs) hold great potential in regenerative medicine, disease modeling and cell biology studies. Reprogramming of mouse and human cells can be achieved through the introduction of transcription factors such as Oct4, Sox2, Klf4, and c-Myc (OSKM), or by chemical stimulation via exposure to small molecules. However, the role of ion compounds in reprogramming has remained relatively unexplored. Herein, we identify iridium (Ir)(III) complexes that enhance iPSC generation by promoting the perinuclear clustering of mitochondria. Mechanistically, Ir(III) complexes promote the nuclear localization of TCA cycle enzyme Pdha1 and increase the cellular acetyl-CoA, leading to chromatin remodeling at pluripotency genes by enhancing histones H3 and H4 acetylation. Our results reveal an important role for Ir(III) complexes in epigenetic regulation of cell fate and suggest a novel approach for iPSC generation.