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The accumulation of free cholesterol in LSEC endolysosomes disrupted Rab7 membrane trafficking and impaired the transport of TLR9 from late endosomes to lysosomes, enhancing activation of the TLR9/inflammasome pathway mediating APAP-induced liver injury

The effect was due to on-target inhibition of GPX4 rather than reduction of GSH levels, as, contrary to the marked reduction in GSH observed with L-buthionine-sulfoximine (BSO), we observed only a small reduction with SCLA2 at 10 M and no change at 1 M (Extended Data Fig

The increase in glycolysis in these cells is substantially rerouted toward the PPP by downregulating the inhibitory sedoheptulose kinase CARKL

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