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The Regulatory Role of Key Metabolites in the Control of Cell Signaling

Authors
  • Milanesi, Riccardo
  • Coccetti, Paola
  • Tripodi, Farida
Type
Published Article
Journal
Biomolecules
Publisher
MDPI AG
Publication Date
Jun 05, 2020
Volume
10
Issue
6
Identifiers
DOI: 10.3390/biom10060862
PMID: 32516886
PMCID: PMC7356591
Source
PubMed Central
Keywords
License
Green

Abstract

Robust biological systems are able to adapt to internal and environmental perturbations. This is ensured by a thick crosstalk between metabolism and signal transduction pathways, through which cell cycle progression, cell metabolism and growth are coordinated. Although several reports describe the control of cell signaling on metabolism (mainly through transcriptional regulation and post-translational modifications), much fewer information is available on the role of metabolism in the regulation of signal transduction. Protein-metabolite interactions (PMIs) result in the modification of the protein activity due to a conformational change associated with the binding of a small molecule. An increasing amount of evidences highlight the role of metabolites of the central metabolism in the control of the activity of key signaling proteins in different eukaryotic systems. Here we review the known PMIs between primary metabolites and proteins, through which metabolism affects signal transduction pathways controlled by the conserved kinases Snf1/AMPK, Ras/PKA and TORC1. Interestingly, PMIs influence also the mitochondrial retrograde response (RTG) and calcium signaling, clearly demonstrating that the range of this phenomenon is not limited to signaling pathways related to metabolism.

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