Molecular Cell
Volume 11, Issue 3, March 2003, Pages 619-633
Journal home page for Molecular Cell

Article
An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress

https://doi.org/10.1016/S1097-2765(03)00105-9Get rights and content
Under an Elsevier user license
open archive

Eukaryotic cells respond to unfolded proteins in their endoplasmic reticulum (ER stress), amino acid starvation, or oxidants by phosphorylating the α subunit of translation initiation factor 2 (eIF2α). This adaptation inhibits general protein synthesis while promoting translation and expression of the transcription factor ATF4. Atf4−/− cells are impaired in expressing genes involved in amino acid import, glutathione biosynthesis, and resistance to oxidative stress. Perk−/− cells, lacking an upstream ER stress-activated eIF2α kinase that activates Atf4, accumulate endogenous peroxides during ER stress, whereas interference with the ER oxidase ERO1 abrogates such accumulation. A signaling pathway initiated by eIF2α phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid sufficiency and resistance to oxidative stress.

Cited by (0)