<i>Mycobacterium tuberculosis</i> phagosome Ca²⁺ leakage triggers multimembrane ATG8/LC3 lipidation to restrict damage in human macrophages.

ABSTRACT: The role of canonical autophagy in controlling Mycobacterium tuberculosis (Mtb), referred to as xenophagy, is understood to involve targeting Mtb to autophagosomes, which subsequently fuse with lysosomes for degradation. Here, we found that Ca²⁺ leakage after Mtb phagosome damage in human macrophages is the signal that triggers autophagy-related protein 8/microtubule-associated proteins 1A/1B light chain 3 (ATG8/LC3) lipidation. Unexpectedly, ATG8/LC3 lipidation did not target Mtb to lysosomes, excluding the canonical xenophagy. Upon Mtb phagosome damage, the Ca²⁺ leakage-dependent ATG8/LC3 lipidation occurred on multiple membranes instead of single or double membranes excluding the noncanonical autophagy pathways. Mechanistically, Ca²⁺ leakage from

SUBMITTER: Chen D 

PROVIDER: S-EPMC11939036 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature