Heritable shifts in redox metabolites during mitochondrial quiescence reprogramme progeny metabolism.
Heritable shifts in redox metabolites during mitochondrial quiescence reprogramme progeny metabolism.
复制标题
线粒体静止重编程后代代谢过程中氧化还原代谢物的可遗传变化。
DOI：
10.1038/s42255-021-00450-3
复制
发表时间：
2021-09
影响因子：
20.8
通讯作者：
Sieber M
中科院分区：
文献类型：
--
作者：
Hocaoglu H;Wang L;Yang M;Yue S;Sieber M
母亲饮食的变化和母亲的代谢缺陷会深刻影响后代的健康和疾病。然而，在细胞水平上诱导初始重编程事件的生化机制在很大程度上仍然是未知的，由于在获得静止卵母细胞的纯群体的限制。在这里，我们表明，过早发病的线粒体呼吸静止（MRQ）的原因重新编程的后代代谢状态。MRQ的过早发作驱动果蝇卵母细胞NAD+水平的降低。卵母细胞中的NAD+耗竭导致胚胎中甲基供体S-腺苷甲硫氨酸（SAM）的甲硫氨酸循环产生减少和H3 K27-me 3水平降低，从而导致后代肠道脂质代谢水平提高。此外，我们发现，在哺乳动物细胞和化疗耐药的人类癌细胞模型中触发细胞静止诱导细胞重编程事件与果蝇中所见相同，表明依赖于静止细胞的系统中存在保守的代谢机制。
Changes in maternal diet and metabolic defects in mothers can profoundly impact progeny health and disease. However, the biochemical mechanisms that induce the initial reprogramming events at the cellular level have remained largely unknown due to limitations in obtaining pure populations of quiescent oocytes. Here, we show that the precocious onset of Mitochondrial Respiratory Quiescence (MRQ) causes a reprogramming of progeny metabolic state. The premature onset of MRQ drives the lowering of Drosophila oocyte NAD+ levels. NAD+ depletion in the oocyte leads to reduced methionine cycle production of the methyl donor S-adenosylmethionine (SAM) in embryos and lower H3K27-me3 levels, resulting in enhanced levels of progeny intestinal lipid metabolism. In addition, we show that triggering cellular quiescence in mammalian cells and chemotherapy-resistant human cancer cell models induces cellular reprogramming events identical to those seen in Drosophila, suggesting a conserved metabolic mechanism in systems reliant on quiescent cells.
登录
查看更多内容
影响因子：
64.5
作者：
Carone BR;Fauquier L;Habib N;Shea JM;Hart CE;Li R;Bock C;Li C;Gu H;Zamore PD;Meissner A;Weng Z;Hofmann HA;Friedman N;Rando OJ
通讯作者：
Rando OJ
影响因子：
14.9
作者：
Contrino S;Smith RN;Butano D;Carr A;Hu F;Lyne R;Rutherford K;Kalderimis A;Sullivan J;Carbon S;Kephart ET;Lloyd P;Stinson EO;Washington NL;Perry MD;Ruzanov P;Zha Z;Lewis SE;Stein LD;Micklem G
通讯作者：
Micklem G
影响因子：
3.7
作者：
Agnoli C;Grioni S;Sieri S;Sacerdote C;Ricceri F;Tumino R;Frasca G;Pala V;Mattiello A;Chiodini P;Iacoviello L;De Curtis A;Panico S;Krogh V
通讯作者：
Krogh V
影响因子：
64.5
作者：
Gkountela S;Zhang KX;Shafiq TA;Liao WW;Hargan-Calvopiña J;Chen PY;Clark AT
通讯作者：
Clark AT
DOI：
10.1073/pnas.0500172102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Anderson, LK;Royer, SM;Hawley, RS
通讯作者：
Hawley, RS