Metabolic signals regulating cell growth versus survival

Project Summary/Abstract: Over the previous funding periods, it was shown that acetyl-CoA and SAM are key signals of cellular metabolic and nutritional state. Acetyl-CoA is an activated carrier of two carbon units, while S-adenosylmethionine is the biological methyl donor in many reactions critical for life – these are two key metabolic currencies used by cells. This application proposes to continue investigating the mechanisms by which acetyl-CoA and SAM function to regulate important cellular pathways in balancing cell growth versus survival in response to metabolic and nutritional state. A combination of genetics, cell biology, and biochemistry will be utilized to elucidate how these sentinel metabolites are compartmentalized intracellularly and influence multiple aspects of the central dogma of molecular biology. Insights from these studies will be informative as to the role of these sentinel metabolites in aging and age-related diseases.