||Monday,7 March 2016, 17:00～
|| Seminar-shitsu 1, IDAC Research building 7F
|| Metabolic homeostasis, redox signaling, and agin
||Joslin Diabetes Center /Harvard Medical School Department of Genetics
|| Hozumi Motohashi （Department of Gene Expression Regulation ext.8550）
|| In the nematode C. elegans, the Nrf/CNC proteins are represented by their ortholog SKN-1. SKN-1 exhibits remarkable functional conservation with mammalian Nrf/CNC proteins, suggesting that C. elegans may have considerable predictive value for investigating how Nrf/CNC proteins function and are regulated. Our work in C. elegans indicates that SKN-1 regulation is surprisingly complex, and is influenced by numerous growth, nutrient, and metabolic signals. We also find that SKN-1 is essential in most pathways capable of extending C. elegans lifespan and healthspan. Two recent studies provide new insights into SKN-1 functions and regulation. We find that SKN-1 plays a major role in lipid metabolism, and seems to be regulated by lipid signals. We also have determined that the endoplasmic reticulum (ER) transmembrane protein IRE-1 functions as a redox-regulated sentinel that activates p38 and SKN-1 in response to certain cytoplasmic stresses. This pathway is conserved in humans, in which it regulates the SKN-1 homolog Nrf2. Our data indicate that the ER functions as a sentinel that monitors stress in the cytoplasm, as well as within the secretory pathway.