Heritable shifts in redox metabolites during mitochondrial quiescence reprogramme progeny metabolism.
Helin HocaogluLei WangMengye YangSibiao YueMatthew H SieberPublished in: Nature metabolism (2021)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- healthcare
- endothelial cells
- public health
- physical activity
- ms ms
- cell cycle arrest
- transcription factor
- pregnant women
- fatty acid
- respiratory tract
- induced pluripotent stem cells
- cell proliferation
- locally advanced
- social media
- body mass index
- neural stem cells
- pluripotent stem cells