Oxidized TRX1 and DPP8/9 stabilize the MIA40-AIFM1 complex during intrinsic apoptosis

After mitochondrial outer membrane permeabilization, oxTRX1 and catalytically active DPP8/9 coordinate redox and proteostasis to stabilize the MIA40-AIFM1 complex, favoring MIA40-bound AIFM1.

• Why it matters: MOMP typically drives immunologically silent intrinsic apoptosis, but how it also restrains the NLRP1 inflammasome and prevents pyroptosis is unclear.
• What they did: Immediately after MOMP, oxTRX1 forms a disulfide with MIA40 Cys4 at the MIA40-AIFM1 interface, and DPP8/9 cleave AK2 to target a competing AIFM1 ligand for degradation; biochemical reconstitution and cryo-EM were used.
• The result: oxTRX1 promotes AIFM1 dimerization and preferentially stabilizes MIA40-AIFM1 over AK2-AIFM1, suggesting post-MOMP remodeling can reinforce NLRP1 restraint and that disruption could trigger pyroptosis.