Apicoplast biogenesis mediated by ATG8 requires the ATG12–ATG5-ATG16L and SNAP29 complexes in Toxoplasma gondii

Structure-Function Relationship for a Divergent Atg8 Protein Required for a Nonautophagic Function in Apicomplexan Parasites

“…We showed that the new effector function of apicomplexan Atg8 requires interactions other than those previously identified for macroautophagy and selective autophagy functions. The LDS, important for interaction with the membrane conjugation machinery, was shown to be important for apicoplast localization of Pf Atg8, and the overall importance of this docking site was also recently demonstrated for Tg Atg8 ( 48 ). On the other hand, mutation of the N-terminal helix did not affect the apicoplast-related function.…”

“…8A to D ). In contrast, a Tg Atg8 mutant where the tyrosine was mutated to an alanine was recently described and shown to be affected in its localization and function at the apicoplast but not in its lipidation ( 48 ). Overall, this suggests that while the UDS may be important for Atg8 function at the apicoplast, the central tyrosine residue found in Apicomplexa species can be replaced by the canonical phenylalanine residue found in mammalian, yeast, or plant Atg8 sequences.…”

“…And most importantly, what are the structural features responsible for the effector function of Pf Atg8? Recent findings on the targeting of Tg Atg8 ( 48 ) suggest that it is translocated to the apicoplast via vesicles in a SNARE-dependent manner, suggesting that the protein may be directly conjugated to the outermost membrane of the apicoplast but to vesicular intermediates first: it was described that the mutation of the UDS abolished Tg Atg8 localization on the apicoplast but not its lipidation (potentially to the trafficking vesicles). This illustrates a potential additional layer of complexity in the apicoplast-specific function of Atg8 and apicomplexan-specific features that are likely driven by sequence and structural determinants.…”

The role of autophagy in idiopathic pulmonary fibrosis: from mechanisms to therapies

“…Then ATG16 L binds to ATG12-ATG5 conjugate noncovalently and dimerizes to compose ATG12-ATG5-ATG16 L complex, which binds to the phagophore membrane then dissociates after autophagosome completion. 49 – 53 Another UBL system involving phagophore expansion is the ATG8/LC3 system. Light Chain 3 (LC3) in mammals is encoded by homologues of the ATG8 gene, which serves as a pivotal indicator of the level of cellular autophagy.…”

An unconventional SNARE complex mediates exocytosis at the plasma membrane and vesicular fusion at the apical annuli in Toxoplasma gondii

“…In T. gondii, only one Qbc SNARE protein (TgSNAP29) has been identified. This protein lacks clear palmitoylation sites in the junction of the two SNARE structural domains, which play a role in apicoplast biogenesis in parasites [14]. There are no clear orthologs of SNAP25 and SNAP23 in T. gondii.…”