近日，荷兰阿姆斯特丹大学Riekelt H. Houtkooper及其研究小组的最新工作发现了一个保守的线粒体-胞质翻译平衡，其联系着两条长寿通路。2020年2月20日，《细胞—代谢》杂志在线发表了这项成果。
Title: A Conserved Mito-Cytosolic Translational Balance Links Two Longevity Pathways
Author: Marte Molenaars, Georges E. Janssens, Evan G. Williams, Aldo Jongejan, Jiayi Lan, Sylvie Rabot, Fatima Joly, Perry D. Moerland, Bauke V. Schomakers, Marco Lezzerini, Yasmine J. Liu, Mark A. McCormick, Brian K. Kennedy, Michel van Weeghel, Antoine H.C. van Kampen, Ruedi Aebersold, Alyson W. MacInnes, Riekelt H. Houtkooper
Abstract: Slowing down translation in either the cytosol or the mitochondria is a conservedlongevity mechanism. Here, we found a non-interventional natural correlation of mitochondrialand cytosolic ribosomal proteins (RPs) in mouse population genetics, suggesting atranslational balance. Inhibiting mitochondrial translation in C. elegans through mrps-5 RNAi repressed cytosolic translation. Transcriptomics integrated with proteomicsrevealed that this inhibition specifically reduced translational efficiency of mRNAsrequired in growth pathways while increasing stress response mRNAs. The repressionof cytosolic translation and extension of lifespan from mrps-5 RNAi were dependent on atf-5/ATF4 and independent from metabolic phenotypes. We found the translational balanceto be conserved in mammalian cells upon inhibiting mitochondrial translation pharmacologicallywith doxycycline. Lastly, extending this in vivo, doxycycline repressed cytosolic translation in the livers of germ-free mice. Thesedata demonstrate that inhibiting mitochondrial translation initiates an atf-5/ATF4-dependent cascade leading to coordinated repression of cytosolic translation,which could be targeted to promote longevity.