xCT, the functional subunit of the system xc(-) encoded by the Slc7a11 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-κB 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.

中文翻译：

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xCT缺乏会通过内质网应激激活的p38-丝裂原激活的蛋白激酶和sut黑素细胞中的mTOR诱导自噬。

xCT是由Slc7a11基因编码的系统xc（-）的功能性亚基，在维持细胞内谷胱甘肽（GSH）水平方面起着重要作用。在先前的研究中，我们已经表明xCT缺乏会诱导OS，OS会通过JNK途径触发细胞凋亡，但是，这种凋亡特征的诱导并不能完全解释xCT缺乏所诱导的细胞死亡。在当前的研究中，我们证明了xCT缺乏的黑色素细胞显示出内质网应激和自噬的激活。xCT缺乏引起的自噬激活是由内质网应激诱导的p38 MAPK和NF-κB通路的激活介导的，并随后抑制了Akt / mTOR / p70S6K生存通路的功能，最终导致了黑素细胞的自噬细胞死亡。