Fig. 8: HOIL-1, PABPC1 and MKRN1 suppress ZAKα-driven disulfidptosis during glucose starvation.

a, The proposed model. Cells in full glucose medium are in homeostasis. During glucose starvation in WT cells, HOIL-1 binds and ubiquitinates PABPC1, which resolves stress and stalled ribosomes by facilitating quality control via MKRN1. In HOIL-1^KO cells, MKRN1 retains PABPC1 binding and quality control is unaffected. HOIL-1^ΔRBR acts as a dominant-negative by binding to PABPC1 and excluding MKRN1 from the complex. Unresolved stalled ribosomes in HOIL-1^ΔRBR cells activate ZAKα, which promotes p38 phosphorylation and ATF4 translation, leading to disulfidptosis.