RRC ID 45825
Author Pang S, Lynn DA, Lo JY, Paek J, Curran SP.
Title SKN-1 and Nrf2 couples proline catabolism with lipid metabolism during nutrient deprivation.
Journal Nat Commun
Abstract Mechanisms that coordinate different metabolic pathways, such as glucose and lipid, have been recognized. However, a potential interaction between amino acid and lipid metabolism remains largely elusive. Here we show that during starvation of Caenorhabditis elegans, proline catabolism is coupled with lipid metabolism by SKN-1. Mutation of alh-6, a conserved proline catabolic enzyme, accelerates fat mobilization, enhances the expression of genes involved in fatty acid oxidation and reduces survival in response to fasting. This metabolic coordination is mediated by the activation of the transcription factor SKN-1/Nrf2, possibly due to the accumulation of the alh-6 substrate P5C, and also requires the transcriptional co-regulator MDT-15. Constitutive activation of SKN-1 induces a similar transcriptional response, which protects animals from fat accumulation when fed a high carbohydrate diet. In human cells, an orthologous alh-6 enzyme, ALDH4A1, is also linked to the activity of Nrf2, the human orthologue of SKN-1, and regulates the expression of lipid metabolic genes. Our findings identify a link between proline catabolism and lipid metabolism, and uncover a physiological role for SKN-1 in metabolism.
Volume 5
Pages 5048
Published 2014-10-6
DOI 10.1038/ncomms6048
PII ncomms6048
PMID 25284427
PMC PMC4205844
MeSH 1-Pyrroline-5-Carboxylate Dehydrogenase / metabolism Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / metabolism* Fatty Acids / chemistry Food HEK293 Cells Humans Lipid Metabolism* Metabolism NF-E2-Related Factor 2 / metabolism* Oxidative Stress Oxygen / chemistry Proline / genetics Proline / metabolism RNA Interference Transcription Factors / metabolism*
IF 12.121
Times Cited 67
C.elegans tm2182