Fig. 8: Scheme of the BAK-mediated unconventional autophagic pathway induced during apoptosis and its role in the control of ATP release.
From: An unconventional autophagic pathway that inhibits ATP secretion during apoptotic cell death
BH3-only activators like BIM or BID engage mitochondrial BAK and trigger its unfolding at the mitochondrial surface. This initial activation step exposes the latch domain (orange), which likely crosses the OMM to bind PHBs and STOM. The resulting protein complex recruits ATG16L1 through interaction between PHBs/STOM and the ATG16L1 WD40 domain to induce formation of single-membrane, unconventional, LC3-positive vesicles. The origin of these vesicles and the detailed mechanisms of their formation remain unclear. The LC3-labelled vesicles sequester ATP and prevent ATP release during the apoptotic process, thus inhibiting the ability of the dying cells to stimulate the innate immune pathways of the recruited phagocytes.
