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. 2022 Jul 8;13(7):591. doi: 10.1038/s41419-022-05044-9

Fig. 7. Schematic view of the mechanism of ferroptosis sensitivity in drug-resistant glioma cells.

Fig. 7

TMZ-resistant cells have higher expression of NRF2 and, consequently, higher levels of ABCC1/MRP1. Upon treatment with TMZ, GSH mediates drug efflux by GSH-conjugate through MRP1 channels enhancing chemotherapy tolerance. Simultaneously, higher levels of MRP1 promote GSH efflux. Upon treatment with Erastin, there was a decrease in GSH synthesis, which is accentuated by GSH efflux through MRP1 promoting GPX4 inactivity and sensitizing these cells to ferroptosis. In contrast, TMZ-sensitive cells can obtain cysteine through compensatory mechanisms to generate GSH synthesis, thus they become resistant to ferroptosis. Created with BioRender.com.