引言
线粒体是细胞能量代谢中心和系统信号中枢,具有强大适应能力,以满足各种生理病理条件下能量需求,确保细胞存活【1】。急性髓系白血病(AML)是最为常见的成人白血病,由造血干祖细胞恶性转化的白血病干细胞发展而来。目前,AML(急性早幼粒细胞白血病除外)治疗手段有限、复发率高、死亡率高,5年总体生存率低<30%。线粒体适应性在AML发生发展及耐药中发挥着重要作用【2】。绝大多数的线粒体蛋白是细胞核DNA编码,这些核编码线粒体蛋白是如何被选择性调控的,目前却知之甚少。
2024年10月1日,武汉大学医学研究院/免疫与代谢前沿科学中心/口腔医学院/泰康生命医学中心张好建课题组,武汉大学中南医院周芙玲课题组,和广州省人民医院/广东省医学科学院孙妍课题组在Cell Stem Cell杂志上发表了题为:Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance的研究论文。该研究发现了RAS响应元件结合蛋白RREB1促进AML发生发展的重要作用,揭示了其同源异构体RREB1S选择性调控核编码线粒体蛋白翻译,促进琥珀酸代谢和线粒体活性,进而维持白血病干细胞干性和药物抗性的分子机制。

参考文献
1. Faubert, B., Solmonson, A., and DeBerardinis, R.J. (2020). Metabolic reprogramming and cancer progression. Science 368, eaaw5473. 10.1126/science.aaw5473.2. Lagadinou, E.D., Sach, A., Callahan, K., Rossi, R.M., Neering, S.J., Minhajuddin, M., Ashton, J.M., Pei, S.S., Grose, V., O'Dwyer, K.M., et al. (2013). BCL-2 Inhibition Targets Oxidative Phosphorylation and Selectively Eradicates Quiescent Human Leukemia Stem Cells. Cell Stem Cell 12, 329-341. 10.1016/j.stem.2012.12.013.3. Signer, R.A.J., Magee, J.A., Salic, A., and Morrison, S.J. (2014). Haematopoietic stem cells require a highly regulated protein synthesis rate. Nature 509, 49-54. 10.1038/nature13035.4. Wang, J., Li, Y., Wang, P., Han, G., Zhang, T., Chang, J., Yin, R., Shan, Y., Wen, J., Xie, X., et al. (2020). Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis. Cell stem cell 27, 81-97.e88. 10.1016/j.stem.2020.04.001.5. Yin, R., Chang, J., Li, Y., Gao, Z., Qiu, Q., Wang, Q., Han, G., Chai, J., Feng, M., Wang, P., et al. (2022). Differential m6A RNA landscapes across hematopoiesis reveal a role for IGF2BP2 in preserving hematopoietic stem cell function. Cell stem cell 29, 149-159.e147. 10.1016/j.stem.2021.09.014.6. Cheng, Y., Gao, Z.Y., Zhang, T.T., Wang, Y.H., Xie, X.Q., Han, G.Q., Li, Y.S., Yin, R., Chen, Y.L., Wang, P.P., et al. (2023). Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenance. Cell stem cell 30, 69-85. 10.1016/j.stem.2022.12.003.https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00322-9责编|探索君
排版|探索君
文章来源|“BioArt”
End