Editors' ChoiceMetabolism

S-nitrosylation links obesity and cell stress

Sci. Signal.  04 Aug 2015:
Vol. 8, Issue 388, pp. ec219
DOI: 10.1126/scisignal.aad1351

Obesity and other diseases are somehow linked to malfunction of the protein-protecting functions of the endoplasmic reticulum (ER). Yang et al. propose a mechanism by which obesity and associated chronic inflammation may be linked to the accumulation of unfolded proteins in the ER. Such stress would normally trigger the process known as the unfolded protein response (UPR). However, obese mice had increased S-nitrosylation of inositol-requiring protein-1 (IRE1α), a ribonuclease that regulates the UPR. Nitrosylated IRE1α had decreased RNAse activity. Expression of an IRE1α mutant protein that could not be nitrosylated in the liver of obese mice improved the UPR and helped restore glucose homeostasis.

L. Yang, E. S. Calay, J. Fan, A. Arduini, R. C. Kunz, S. P. Gygi, A. Yalcin, S. Fu, G. S. Hotamisligil, S-Nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction. Science 349, 500–506 (2015). [Abstract] [Full Text]