Figure 1.

Role of ATG5 in lysosomal quality control and secretion activities. In WT cells, damaged lysosomes are repaired by ESCRT machinery including PDCD6IP/ALIX, which is absent in ATG5-deficient cells. The defective membrane repair leads to increased lysosomal exocytosis. ATG5 absence favors the formation of the alternative conjugate ATG12–ATG3, which sequesters PDCD6IP/ALIX making it unavailable to repair lysosomes and at the same time promotes secretion of exosomes. In neutrophils, ATG5 deficiency leads to increased degranulation, elevated release of EVPs, and a heightened state of activation. In the context of M. tuberculosis infection (not depicted) this contributes to excessive neutrophilic inflammation and exacerbated tuberculosis pathogenesis.