Figure 8. Proposed model for verteporfin-mediated inhibition of autophagosome formation involving p62 crosslink products.

As p62 oligomers are recruited to the autophagosome membrane, they become oxidized and crosslinked to each other due to low-level singlet oxygen generation by verteporfin. This crosslinking event interferes with p62 binding to polyubiquitinated cargo, but does not affect LC3 binding. The generation of large p62 crosslink products with impaired function either physically disrupts proper autophagosome elongation and closure or it interferes with the function of other molecules necessary for completely autophagosome formation.