Portal de Periódicos da CAPES

S-Nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction

2015; American Association for the Advancement of Science; Volume: 349; Issue: 6247 Linguagem: Inglês

10.1126/science.aaa0079

1095-9203

Ling Yang, Ediz S. Calay, Jason Fan, Alessandro Arduini, Ryan C. Kunz, Steven P. Gygi, Abdullah Yalçın, Suneng Fu, Gökhan S. Hotamışlıgil,

Autophagy in Disease and Therapy

S-nitrosylation links obesity and cell stress 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. The modified IRE1α had decreased RNAse activity. The authors expressed an IRE1α mutant protein that could not be nitrosylated in the liver of obese mice. This approach improved the UPR and helped restore glucose homeostasis. Science , this issue p. 500