Individual Atg8 paralogs exhibit unique properties in streptococcus pneumoniae-induced hierarchical autophagy.

ABSTRACT

Individual Atg8 (autophagy related 8) paralogs, comprising MAP1LC3A/LC3A, LC3B, LC3C, GABARAP, GABARAPL1 and GABARAPL2/GATE16, play a crucial role in canonical macroautophagy/autophagy. However, their functions remain unclear owing to functional redundancy. In a previous study, we reported that intracellular Streptococcus pneumoniae triggers hierarchical autophagy in response to bacterial infection. This process commences with the induction of conjugation of Atg8 paralogs (Atg8s) to single membranes (CASM), followed by CASM shedding and subsequent induction of xenophagy. In our recent study, we performed functional analysis of Atg8s during pneumococci-induced hierarchical autophagy. Our findings suggest that LC3A and GABARAPL1 are crucial for CASM induction, whereas GABARAPL2 and GABARAP play sequential roles in CASM shedding and subsequent induction of xenophagy, respectively.Abbreviation Atg8 autophagy related 8; Atg8s Atg8 paralogs; CASM conjugation of Atg8s to single membranes; mpi minutes post-infection; mpi minutes post-infection; PcAV pneumococci-containing autophagic vesicles; PcLV LC3-associated phagosome (LAPosome)-like vacuole; PcV pneumococci-containing vesicles; Sp S. pneumoniae.