重编程
生物
NAD+激酶
卵母细胞
细胞生物学
线粒体
新陈代谢
呼吸链
表观基因组
生物化学
组蛋白
遗传学
胚胎
细胞
基因
DNA甲基化
基因表达
酶
作者
Helin Hocaoglu,Lei Wang,Mei Yang,Sibiao Yue,Matthew Sieber
标识
DOI:10.1038/s42255-021-00450-3
摘要
Changes in maternal diet and metabolic defects in mothers can profoundly affect health and disease in their progeny. However, the biochemical mechanisms that induce the initial reprogramming events at the cellular level have remained largely unknown owing to limitations in obtaining pure populations of quiescent oocytes. Here, we show that the precocious onset of mitochondrial respiratory quiescence causes a reprogramming of progeny metabolic state. The premature onset of mitochondrial respiratory quiescence 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 in embryos and lower levels of histone H3 lysine 27 trimethylation, resulting in enhanced intestinal lipid metabolism in progeny. 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.
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