On August 30th 2018, Cell Metabolism published the research results of Liu Xingguo's group from Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, “Short-Term Mitochondrial Permeability Transition Pore Opening Modulates Histone Lysine Methylation at the Early Phase of Somatic Cell Reprogramming”.
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. The Liu Xingguo research group 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. 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. This findings represent a novel mitochondria-to-nucleus pathway in cell fate determination by mPTP-mediated epigenetic regulation.
This work was financially supported by The National Key Research and Development Program of China, Guangzhou regenerative medicine and health Guangdong laboratory, the National Natural Science Foundation projects of China, the foundation of Guangdong Province and Guangzhou city.