Abstract
Cellular metabolism has emerged as a major biological node governing cellular behaviour. Metabolic pathways fuel cellular energy needs, providing basic chemical molecules to sustain cellular homeostasis, proliferation and function. Changes in nutrient consumption or availability therefore can result in complete reprogramming of cellular metabolism towards stabilizing core metabolite pools, such as ATP, S-adenosyl methionine, acetyl-CoA, NAD/NADP and α-ketoglutarate. Because these metabolites underlie a variety of essential metabolic reactions, metabolism has evolved to operate in separate subcellular compartments through diversification of metabolic enzyme complexes, oscillating metabolic activity and physical separation of metabolite pools. Given that these same core metabolites are also consumed by chromatin modifiers in the establishment of epigenetic signatures, metabolite consumption on and release from chromatin directly influence cellular metabolism and gene expression. In this Review, we highlight recent studies describing the mechanisms determining nuclear metabolism and governing the redistribution of metabolites between the nuclear and non-nuclear compartments.
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Acknowledgements
We thank members of the laboratory of R.M. for helpful discussions. Research in the laboratory of R.M. is supported by US NIH grants (R33ES025638, R01GM128448, R21ES027931 and R01CA235412) and CDMRP (W81XWH-17-1-0517). R.M. is supported as the Laurel Schwartz Endowed Professor of Oncology at the MGH Cancer Center/Harvard Medical School. R.B. is supported by postdoctoral fellowship LT-000311/2019-l from the Human Frontier Science Program. G.G.S. is supported by an MGH Cancer Center Excellence Award.
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R.M., G.G.S. and R.B. wrote, revised and approved the final version; R.B. prepared the figures.
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Boon, R., Silveira, G.G. & Mostoslavsky, R. Nuclear metabolism and the regulation of the epigenome. Nat Metab 2, 1190–1203 (2020). https://doi.org/10.1038/s42255-020-00285-4
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DOI: https://doi.org/10.1038/s42255-020-00285-4
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