On August 30, the international academic journal Cell Metabolism published its latest research results from Liu Xingguo Research Group of the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences, "Short-term Mitochdrial Permeability Embryo Sok E Quice Stone Lysine Methylation at The Early Phase of The End of The Dmitria Through Conversion Hole Short-Term Open Regulatory Control Cell-Cells Reprogramming.
the study found that in the early stages of somatic cell reprogramming as induced pluripotent stem cells (iPSC), mitochondrial permeability conversion holes (Mitochondrial Permeability Transition Pore, mPTP) were opened for a short time, which facilitated reprogramming by regulating epigenetic changes in the methylation of histones in the nucleus of cells.
this is the first report of mitochondrial pores that regulate the fate of cells through epigenetics.
mitochondria play an important role in the fate of pluripotent stem cells.
the number of mitochondria of pluripotent stem cells and the degradation of the internal crucibles compared to somatic cells, resulting in the remodeling of the morphological structure of the mitochondria during pluripotent acquisition (Xingguo Liu, Autophagy, 2017).
function, international research focuses on online granulocyte metabolism, many metabolic intermediates can regulate epigenetic modification, and then determine the fate of pluripotent stem cells.
Liu Xingguo's research team took a different approach, reporting in Cell Alysm in 2016 that mitochondrial ion signalmitol signalmitol seismost (mitoflash) was reprogrammed through DNA demethylation regulation.
the new direction of the apparent genetic control of the online granulation ion signal, Liu Xingguo group carried out a continuous in-depth study, focusing on the mitochondrial and cytoplasmic communication of the important channel - mitochondrial permeable conversion hole, revealing a new model of cytoplasmic regulation of the nucleus.
mitochondrial permeable conversion hole is a histone complex that exists between the outer membranes of the mitochondria and is a nonspecific channel.
these holes dotted with online granules, the opening and closing of the channel is essential, so that the cells also die: permanent opening causes cell death (Xingguo Liu, Hepatology, 2015);
the instantaneous opening of the mitochondrial permeable conversion hole, also known as mitochondrial flashing, however, it has been unclear whether and how it regulates the epigenetics of the nucleus.
somatic cell reprogramming technology not only greatly promotes the development of regenerative medicine, but also provides an ideal model for the study of the mechanism of cell destiny decision. Through this model
, liu Xingguo's team used calchelit/cobalt technology to observe the openness of the mitochondrial permeable conversion hole in real time, and was surprised to find that the opening of the channel increased sharply and then decreased rapidly in the early stages of Yamanaka factor addition to somatic cells.
this high openness is due to the sudden increase in the instantaneous opening of the "mitochondrial flicker" frequency, which is conducive to reprogramming somatic cells for induced pluripotent stem cells.
systematic histone methylation tests found that "mitochondrial flickering" can specifically lead to significant demethylation of H3K9me2 and H3K27me3 (the two major barriers of reprogramming) and reduce the binding of the two to polypotent genes. further mechanism studies
show that "mitochondrial flicker" regulates methylation levels of H3K9me2 and H3K27me3 through a dual pathway of mass and mass: first, the expression of histone demethylated enzyme PHF8 through miR-101c;
mitochondria and nucleus are two organelles containing genetic material in mammalian cells, and the interaction between the two is crucial to the fate of the cell.
the study revealed for the first time the activation of the permeable conversion hole of the mitochondria, which opens the cell nucleus reprogrammed histone methylation barrier;
this discovery is a new model of mitochondrial signal ingestion of cell nuclear epigenetics, which may play an important role in cell transformation and individual development, and provides new ideas for the development of cell destiny conversion technology.
the research was supported by national key research and development projects, the Chinese Academy of Sciences, the National Natural Science Foundation, Guangdong Province and Guangzhou.