Xiao-Nan Wu, Jia-Yuan Li, Qi He, Bo-Qun Li, Yao-Hui He, Xu Pan, Ming-Yue Wang, Rui Sang, Jian-Cheng Ding, Xiang Gao, Zhen Wu, Wen Liu
High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development...
January 9, 2024: Proceedings of the National Academy of Sciences of the United States of America