IMPC: Investigation into the function of pyrroline 5-carboxylate reductase 1 (PYCR1) in metabolic homeostasis

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The metabolism of cells is tightly controlled so that nutrients taken up from the outside are used efficiently, and only when necessary. This level of control requires checks and balances that link different metabolic activities - for example the metabolism of sugars and amino acids - ensuring normal cell function. One key aspect of metabolism that is critical for normal cell function is known as redox homeostasis - the balance of pro- and anti-oxidants. An aberrant redox status in a cell can lead to its malfunction and drive changes that may result in disease. Some diseases known to be linked to changes in redox homeostasis are cancer, diabetes and chronic inflammation. We have recently discovered that our understanding of how the enzyme known as pyrroline 5-carboxylate reductase 1 (PYCR1) functions, may be incorrect. This enzyme is responsible for making an amino acid called proline, but in doing so, it influences the redox state of the cell. Although we've previously thought that the main function of this enzyme was to make proline, it may actually be to react to changes in cell redox to try and keep the metabolism of the cell healthy.This proposal will provide the first physiological information to support our hypothesis - that PYCR1 is a critical enzyme in the response to changes in the redox environment of cell. The data that comes out of this research will provide the building blocks - both data and animal model - for a bigger grant application to investigate this hypothesis more fully.