ATG7 is dispensable for LC3-PE conjugation in thioglycolate-elicited mouse peritoneal macrophages

Thioglycolate-elicited macrophages exhibit abundant conjugation of LC3 with PE (LC3-II). Among other autophagy-related (ATG) proteins, it is proposed that, like in yeast, both ATG5 and ATG7 are essential for LC3 conjugation. Using atg5-deficient ((-/-)) and atg7(-/-) macrophages, we provide evidence that loss of ATG5 but not of ATG7 resulted in LC3-II depletion. Accumulation of LC3-II in elicited atg7(-/-) macrophages in response to bafilomycin A(1) validated these data. Furthermore, complete loss of ATG3 in atg7(-/-) macrophages demonstrated that ATG7 and ATG3 are dispensable for LC3-PE conjugation. In contrast to thioglycolate-elicited macrophages, naive peritoneal and bone marrow-derived atg7(-/-) macrophages exhibited no LC3-II, even under inflammatory stimuli in vitro. Hence, the macrophage metabolic status dictates the level of LC3-PE conjugation with a supportive but nonessential role of ATG7, disclosing the eukaryotic exception from the LC3 lipidation model based on yeast data.