Abstract
Availability of the amino acid methionine shows remarkable effects on the physiology of individual cells and whole organisms. For example, most cancer cells, but not normal cells, are hyper dependent on high flux through metabolic pathways connected to methionine, and diets restricted for methionine increase healthy lifespan in model organisms. Methionine’s impact on physiology goes beyond its role in initiation of translation and incorporation in proteins. Many of its metabolites have a major influence on cellular functions including epigenetic regulation, maintenance of redox balance, polyamine synthesis, and phospholipid homeostasis. As a central component of such essential pathways, cells require mechanisms to sense methionine availability. When methionine levels are low, cellular response programs induce transcriptional and signaling states to remodel metabolic programs and maintain methionine metabolism. In addition, an evolutionary conserved cell cycle arrest is induced to ensure cellular and genomic integrity during methionine starvation conditions. Methionine and its metabolites are critical for cell growth, proliferation, and development in all organisms. However, mechanisms of methionine perception are diverse. Here we review current knowledge about mechanisms of methionine sensing in yeast and mammalian cells, and will discuss the impact of methionine imbalance on cancer and aging.
Highlights
Cells must be able to properly assess their environment for the availability of resources required for growth
Methionine restricted growth conditions are reflected in the intracellular is present, two molecules of the amino acid are bound by homo-dimeric CASTOR1 causdecrease of SAM levels [48]
SAMTOR orthologs are present in most animal kingdoms, interestingly none can be Throughout different eucaryotic species, caloric restriction appears to positively infound in Saccharomyces cerevisiae [36]
Summary
Cells must be able to properly assess their environment for the availability of resources required for growth. Systems that sense the abundance of essential nutrients are needed to signal a potential supply deficit to coordinate metabolism and growth. The sulfur containing amino acid methionine presents a key metabolite with major influence on translation, epigenetics, cell proliferation, and various signaling cascades. Sensing the status of methionine metabolism and some of its metabolites is critical for cellular, epigenetic, and genomic integrity. Levels, rather than methionine, seem to be sensed to monitor the status of methionine metabolism. Epigenetic regulation, nucleotide biosynthesis, and membrane lipid homeostasis depend on the abundance of SAM, a key product of methionine metabolism and the major methyl-group donor in cells. When levels of methionine or SAM are low, cellular response programs are activated to combat these conditions. Respond to methionine starvation conditions, how cells try to overcome them to ensure organismal health, and the significance of methionine and SAM in the context of aging and cancer
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