线粒体通透性转换孔（mPTP）是存在于线粒体内外膜之间的由蛋白复合体组成的非特异性通道。mPTP在细胞的生存、凋亡等细胞活动中扮演着重要角色，然而它在细胞命运决定中的作用尚不清楚。在前期研究中，我们发现在重编程早期，线粒体mPTP开放能激活氧信号并通过组蛋白去甲基化酶PHF8促进重编程（Cell Metabolism, 2016；2018）。在本项目中我们将全面检测mPTP开放激活的氧信号及下游的表观遗传学调控，进一步研究mPTP开放促进PHF8表达机制，包括1）重编程早期mPTP开放激活的氧信号；2）mPTP开放通过氧信号对PHF8启动子的去甲基化调控及机制；3）mPTP开放促进PHF8表达的氧相关信号通路。通过本研究将阐述重编程早期线粒体mPTP开放激活的表观遗传调控和信号通路，揭示重编程早期线粒体mPTP开放调控PHF8表达的机制，有望为线粒体在细胞命运转变中的功能研究提供理论基础。

Mitochondrial permeability transition pore (mPTP) is a protein pore that is formed through the inner and outer membrane of the mitochondria. mPTP has been reported to play important roles in cell survival and apoptosis, however, its role in cell fate determination is not clear. Our previous studies found that mPTP opening activated oxygen signaling and improved reprogramming through histone demethylase PHF8 (Cell Metabolism, 2016；2018). In this project, we will investigate all oxygen signaling and epigenetics changes to study the mechanism of mPTP enhanced PHF8 expression. The research includes: (1) investigation of oxygen signaling activated by mPTP opening at the early phase of reprogramming; (2) demethylation of PHF8 promoter by mPTP opening and its mechanisms; (3) investigation of the mPTP opening activated oxygen signaling pathways which enhance PHF8 expression. Our research will elaborate the epigenetics changes and signaling pathways which activated by mPTP opening, and reveal the mechanism of mPTP opening increased PHF8 expression at the early phase of reprogramming. Our research will provide a theoretical basis for the study of mitochondrial function in cell fate transition.