Double duty of Atg9 self-association in autophagosome biogenesis.
The understanding of the membrane flow process during autophagosome formation is essential to illuminate the role of autophagy under various disease-causing conditions. Atg9 is the only identified integral membrane protein required for autophagosome formation, and it is thought to cycle between the membrane sources and the phagophore assembly site (PAS). Thus, Atg9 may play an important role as a membrane carrier. We report the self-interaction of Atg9 and generate an Atg9 mutant that is defective in this interaction. This mutation results in abnormal autophagy, due to altered phagophore formation as well as inefficient membrane delivery to the PAS. Based on our analyses, we discuss a model suggesting dual functions for the Atg9 complex: by reversibly binding to another Atg9 molecule, Atg9 can both promote lipid transport from the membrane origins to the PAS, and also help assemble an intact phagophore membrane.
He
Congcong
C
Life Sciences Institute, and Departments of Molecular, Cellular and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Baba
Misuzu
M
Klionsky
Daniel J
DJ
D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D003593:Cytoplasm / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic
C434065:ATG9 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins