Short-Term Mitochondrial Permeability Transition Pore Opening Modulates Histone Lysine Methylation at the Early Phase of Somatic Cell Reprogramming

Cell Metabolism
Zhongfu YingXingguo Liu

Abstract

Reprogramming of somatic cells to induced pluripotent stem cells reconfigures chromatin modifications. Whether and how this process is regulated by signals originating in the mitochondria remain unknown. Here we show that the mitochondrial permeability transition pore (mPTP), a key regulator of mitochondrial homeostasis, undergoes short-term opening during the early phase of reprogramming and that this transient activation enhances reprogramming. In mouse embryonic fibroblasts, greater mPTP opening correlates with higher reprogramming efficiency. The reprogramming-promoting function of mPTP opening is mediated by plant homeodomain finger protein 8 (PHF8) demethylation of H3K9me2 and H3K27me3, leading to reduction in their occupancies at the promoter regions of pluripotency genes. mPTP opening increases PHF8 protein levels downstream of mitochondrial reactive oxygen species production and miR-101c and simultaneously elevates levels of PHF8's cofactor, α-ketoglutarate. Our findings represent a novel mitochondria-to-nucleus pathway in cell fate determination by mPTP-mediated epigenetic regulation.

Citations

May 22, 2019·Cold Spring Harbor Perspectives in Biology·Benjamin WacquierGeneviève Dupont
Feb 7, 2020·Biological Reviews of the Cambridge Philosophical Society·Meghan A CastelliClare E Holleley
Apr 23, 2020·Cellular and Molecular Life Sciences : CMLS·Zhenhua Yang, Hao Jiang
Sep 11, 2020·Oxidative Medicine and Cellular Longevity·Jialiang LiangPing Zhu
Jan 10, 2021·Redox Biology·Ildiko SzaboLucia Biasutto
Jul 1, 2020·Journal of Molecular Cell Biology·Yang LiuXingguo Liu
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Andrea UrbaniIldikò Szabò
Apr 9, 2021·The International Journal of Biochemistry & Cell Biology·Lin XieYideng Jiang
Oct 23, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·H Alves-FigueiredoG García-Rivas

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Fate Specification

Cell fate specification is determined by complex signal transduction pathways including Notch and the Sonic hedgehog signaling pathway. Here is the latest research on regulation of cell fate determination.