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.

母亲饮食的变化和母亲的代谢缺陷会深刻影响其后代的健康和疾病。然而，由于获得纯静止卵母细胞群的局限性，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未知。在这里，我们表明线粒体呼吸静止的早熟会导致后代代谢状态的重新编程。线粒体呼吸静止的过早开始导致果蝇卵母细胞 NAD ⁺水平的降低。卵母细胞中的NAD ⁺耗竭导致甲基供体S的甲硫氨酸循环产生减少胚胎中的腺苷甲硫氨酸和较低水平的组蛋白 H3 赖氨酸 27 三甲基化，导致后代肠道脂质代谢增强。此外，我们表明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会诱导与果蝇中观察到的相同的细胞重编程事件，表明依赖静止细胞的系统中存在保守的代谢机制。