Exocyst Subcomplex Functions in Autophagosome Biogenesis by Regulating Atg9 Trafficking

• Published in: Journal of molecular biology 2019-07, Vol.431 (15), p.2821-2834
• Main Authors: Singh, Sunaina, Kumari, Ruchika, Chinchwadkar, Sarika, Aher, Amol, Matheshwaran, Saravanan, Manjithaya, Ravi
• Format: Article
• Language: English
• Subjects: Atg9 trafficking; Autophagosome biogenesis; Autophagosomes - metabolism; Autophagy; Autophagy-Related Proteins - metabolism; Exocyst; Membrane Proteins - metabolism; Multiprotein Complexes - metabolism; Mutation; Protein Subunits - metabolism; Protein Transport; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Tethers
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2019.04.048

During autophagy, double-membrane vesicles called autophagosomes capture and degrade the intracellular cargo. The de novo formation of autophagosomes requires several vesicle transport and membrane fusion events which are not completely understood. We studied the involvement of exocyst, an octameric tethering complex, which has a primary function in tethering post-Golgi secretory vesicles to plasma membrane, in autophagy. Our findings indicate that not all subunits of exocyst are involved in selective and general autophagy. We show that in the absence of autophagy specific subunits, autophagy arrest is accompanied by accumulation of incomplete autophagosome-like structures. In these mutants, impaired Atg9 trafficking leads to decreased delivery of membrane to the site of autophagosome biogenesis thereby impeding the elongation and completion of the autophagosomes. The subunits of exocyst, which are dispensable for autophagic function, do not associate with the autophagy specific subcomplex of exocyst. [Display omitted] •A subcomplex of exocyst is involved in autophagosome biogenesis.•Incompletely formed autophagosomes are formed in the absence of functional exocyst.•Autophagosome biogenesis is affected in exocyst mutants due to diminished membrane supply by Atg9 vesicles.•The exocyst subcomplex mediates the Atg9 vesicles tethering at PAS.