Fig. 8: Model: loss of MPI leads to cell death in AML through inhibition of FAO leading to PUFA accumulation and ferroptosis. | Nature Communications

Fig. 8: Model: loss of MPI leads to cell death in AML through inhibition of FAO leading to PUFA accumulation and ferroptosis.

From: Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death

Fig. 8: Model: loss of MPI leads to cell death in AML through inhibition of FAO leading to PUFA accumulation and ferroptosis.The alternative text for this image may have been generated using AI.

A model of the proposed mechanism. WT AML cells treated with both standard and FLT3 inhibitor therapies are able to escape cell death by adapting their metabolism, in this case by switching from glycolysis to fatty acid oxidation. Conversely treated AML cells with depleted MPI have preferential activation of the ATF6 arm of the unfolded proteins response which inhibits fatty acid oxidation. This is paired with increased uptake of fatty acids, particularly polyunsaturated fatty acids, by MPI depleted cells. Both these effects lead to intracellular accumulation of PUFAs and PUFAs containing lipid species. These undergo lipid peroxidation leading to ferroptotic cell death in these cells.

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