4.7 Article

Metabolic decisions in development and disease-a Keystone Symposia report

Journal

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Volume 1506, Issue 1, Pages 55-73

Publisher

WILEY
DOI: 10.1111/nyas.14678

Keywords

cell signaling; development; inborn errors of metabolism; metabolism; metabolome; stem cell differentiation

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There is a growing recognition of the importance of metabolism in cell signaling and decision making, with precise metabolic control being essential in development. The metabolic profile of cells is cell-type specific and can change during differentiation or tumorigenesis. Recent evidence suggests that metabolites play a direct role in promoting or inhibiting changes in cell state, linking metabolic pathways with cell signaling pathways through various mechanisms.
There is an increasing appreciation for the role of metabolism in cell signaling and cell decision making. Precise metabolic control is essential in development, as evident by the disorders caused by mutations in metabolic enzymes. The metabolic profile of cells is often cell-type specific, changing as cells differentiate or during tumorigenesis. Recent evidence has shown that changes in metabolism are not merely a consequence of changes in cell state but that metabolites can serve to promote and/or inhibit these changes. Metabolites can link metabolic pathways with cell signaling pathways via several mechanisms, for example, by serving as substrates for protein post-translational modifications, by affecting enzyme activity via allosteric mechanisms, or by altering epigenetic markers. Unraveling the complex interactions governing metabolism, gene expression, and protein activity that ultimately govern a cell's fate will require new tools and interactions across disciplines. On March 24 and 25, 2021, experts in cell metabolism, developmental biology, and human disease met virtually for the Keystone eSymposium, Metabolic Decisions in Development and Disease. The discussions explored how metabolites impact cellular and developmental decisions in a diverse range of model systems used to investigate normal development, developmental disorders, dietary effects, and cancer-mediated changes in metabolism.

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