Inhibited autophagy blocks xCT transport to the membrane

I think this is quite an important finding: When autophagy is inhibited for any reason, the cystine antiporter (SLC7A11 or xCT) can’t be transported to the membrane and remains in the cytosol, despite strong upregulation in response to Nrf2.

The outcome is: the cell can’t get enough cystine to make cysteine, which results in increased oxidative stress despite Nrf2 activation.

These results indicate that autophagy inhibition does not affect the expression of Nrf2 and its downstream target genes SLC7A11 and GPX-4, but does significantly inhibit the correct localization of SLC7A11 in cells and its cysteine transport function. (R1)