xCT deficiency induces autophagy via endoplasmic reticulum stress activated p38-mitogen-activated protein kinase and mTOR in sut melanocytes

xCT, the functional subunit of the system xc-encoded by the Slc7a1 1 gene, plays an important role in maintaining intracellular glutathione (GSH) levels. In previous study, we have indicated that xCT deficiency induces OS and that OS triggers apoptosis through JNK pathway, however, this induction of apoptotic features did not fully explain the cell death induced by xCT deficiency. In the current study, we demonstrated that sut melanocytes of xCT deficiency showed activation of both ER stress and autophagy. And that the activation of autophagy by xCT deficiency was mediated by ER stress induced activation of p38 MAPK and NF-kappa B pathways and subsequently inhibited functions of Akt/mTOR/p70S6K survival pathways, ultimately led to autophagic cell death of sut melanocytes. Our novel results provided important insights into understanding the mechanism associated with xCT deficiency. (C) 2016 Elsevier GmbH. All rights reserved.