title: NBR1 acts as an autophagy receptor for peroxisomes.
abstract: Selective macro-autophagy is an intracellular process by which large cytoplasmic materials are selectively sequestered and degraded in the lysosomes. Substrate selection is mediated by ubiquitylation and recruitment of ubiquitin-binding autophagic receptors such as p62, NBR1, NDP52 and Optineurin. Although it has been shown that these receptors act cooperatively to target some types of substrates to nascent autophagosomes, their precise roles are not well understood. We examined selective autophagic degradation of peroxisomes (pexophagy), and found that NBR1 is necessary and sufficient for pexophagy. Mutagenesis studies of NBR1 showed that the amphipathic α-helical J domain, the ubiquitin-associated (UBA) domain, the LC3-interacting region and the coiled-coil domain are necessary to mediate pexophagy. Strikingly, substrate selectivity is partly achieved by NBR1 itself by coincident binding of the J and UBA domains to peroxisomes. Although p62 is not required when NBR1 is in excess, its binding to NBR1 increases the efficiency of NBR1-mediated pexophagy. Together, these results suggest that NBR1 is the specific autophagy receptor for pexophagy.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Deosaran
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Larsen
authors.forename: Rong
authors.initials: R
authors.lastname: Hua
authors.forename: Graeme
authors.initials: G
authors.lastname: Sargent
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Wang
authors.forename: Sarah
authors.initials: S
authors.lastname: Kim
authors.forename: Trond
authors.initials: T
authors.lastname: Lamark
authors.forename: Miluska
authors.initials: M
authors.lastname: Jauregui
authors.forename: Kelsey
authors.initials: K
authors.lastname: Law
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lippincott-Schwartz
authors.forename: Andreas
authors.initials: A
authors.lastname: Brech
authors.forename: Terje
authors.initials: T
authors.lastname: Johansen
authors.forename: Peter K
authors.initials: PK
authors.lastname: Kim
mesh_terms: D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D011506:Proteins / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C549756:NBR1 protein, human; D011506:Proteins