Faa1 membrane binding drives positive feedback in autophagosome biogenesis via fatty acid activation

Abstract

Autophagy serves as a stress response pathway by mediating the degradation of cellular material within lysosomes. In autophagy, this material is encapsulated in double-membrane vesicles termed autophagosomes, which form from precursors referred to as phagophores. Phagophores grow by lipid influx from the endoplasmic reticulum into Atg9-positive compartments and local lipid synthesis provides lipids for their expansion. How phagophore nucleation and expansion are coordinated with lipid synthesis is unclear. Here, we show that Faa1, an enzyme activating fatty acids, is recruited to Atg9 vesicles by directly binding to negatively charged membranes with a preference for phosphoinositides such as PI3P and PI4P. We define the membrane-binding surface of Faa1 and show that its direct interaction with the membrane is required for its recruitment to phagophores. Furthermore, the physiological localization of Faa1 is key for its efficient catalysis and promotes phagophore expansion. Our results suggest a positive feedback loop coupling phagophore nucleation and expansion to lipid synthesis.

Current status, challenges and prospects of antifouling materials for oncology applications

“…Polyzwitterions can be fabricated into various structural forms such as brushes ( 37 ), films ( 38 ), hydrogels ( 39 ), particles ( 40 ), membranes ( 41 ), and coatings ( 42 ), each serving different functions like antifouling ( 43 ), stimuli responsiveness ( 44 ), lubrication ( 45 ), self-healing ( 46 ), antibacterial properties ( 43 ), and biosensing capabilities ( 47 ). Because of their high tolerance to extremely salty conditions, these materials have the potential to be used in various applications such as ionomers ( 48 ), fibers ( 49 ), rheology modifiers ( 50 ), drug/gene delivery vehicles ( 51 ), analogues of biological structures ( 52 ), and anti-fouling materials ( 53 ). Zwitterionic materials not only have excellent antifouling properties but also improve biocompatibility, decrease immunological response, facilitate cellular uptake of chemical drugs and genes, and extend circulation time ( 54 ).…”