title: Peroxisomal Atg37 binds Atg30 or palmitoyl-CoA to regulate phagophore formation during pexophagy.
abstract: Autophagy is a membrane trafficking pathway that sequesters proteins and organelles into autophagosomes. The selectivity of this pathway is determined by autophagy receptors, such as the Pichia pastoris autophagy-related protein 30 (Atg30), which controls the selective autophagy of peroxisomes (pexophagy) through the assembly of a receptor protein complex (RPC). However, how the pexophagic RPC is regulated for efficient formation of the phagophore, an isolation membrane that sequesters the peroxisome from the cytosol, is unknown. Here we describe a new, conserved acyl-CoA-binding protein, Atg37, that is an integral peroxisomal membrane protein required specifically for pexophagy at the stage of phagophore formation. Atg30 recruits Atg37 to the pexophagic RPC, where Atg37 regulates the recruitment of the scaffold protein, Atg11. Palmitoyl-CoA competes with Atg30 for Atg37 binding. The human orthologue of Atg37, acyl-CoA-binding domain containing protein 5 (ACBD5), is also peroxisomal and is required specifically for pexophagy. We suggest that Atg37/ACBD5 is a new component and positive regulator of the pexophagic RPC.
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, and 2 San Diego Center for Systems Biology, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Taras Y
authors.initials: TY
authors.lastname: Nazarko
authors.forename: Katharine
authors.initials: K
authors.lastname: Ozeki
authors.forename: Andreas
authors.initials: A
authors.lastname: Till
authors.forename: Geetha
authors.initials: G
authors.lastname: Ramakrishnan
authors.forename: Pouya
authors.initials: P
authors.lastname: Lotfi
authors.forename: Mingda
authors.initials: M
authors.lastname: Yan
authors.forename: Suresh
authors.initials: S
authors.lastname: Subramani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D000071058:Huntingtin Protein; D007091:Image Processing, Computer-Assisted; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000235:genetics / Q000378:metabolism*; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000502:physiology*; D010843:Pichia / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D000071456:Sequestosome-1 Protein
chemical_list: C548478:ACBD5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D005656:Fungal Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D010171:Palmitoyl Coenzyme A