The insufficiency of ATG4A in macroautophagy
Nathan Nguyen, Taryn J. Olivas, Antonio Mires, Jiaxin Jin, Shenliang Yu, Lin Luan, Shanta Nag, Karlina J. Kauffman, Thomas J. Melia
Abstract
reconstitution systems in which we controlled the attachment of LC3/GABARAP members and discovered a role for a C-terminal LC3-interacting region on ATG4A in regulating its access to LC3/GABARAP. We then used a gene-edited cell line in which all four ATG4 proteases have been knocked out to establish that ATG4A is insufficient to support autophagy and is unable to support GABARAP proteins removal from the membrane. As a result, GABARAP proteins accumulate on membranes other than mature autophagosomes. These results suggest that to support efficient production and consumption of autophagosomes, additional factors are essential including possibly ATG4B itself or one of its proteolytic products in the LC3 family.