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NBR1 acts as an autophagy receptor for peroxisomes
Elizabeth Deosaran, Kenneth B. Larsen, Rong Hua, Graeme Sargent, Yuqing Wang, Sarah Kim, Trond Lamark, Miluska Jauregui, Kelsey Law, Jennifer Lippincott-Schwartz, Andreas Brech, Terje Johansen, Peter K. Kim


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.


  • Funding

    This work was funded by an operating grant from the Canadian Institutes of Health Research [grant number MOP-111164 to P.K.K.]; an infrastructure grant from Canada Foundation for Innovation [grant number 23584 to P.K.K.]; the Ontario Research Fund [grant number 23584 to P.K.K.]; the Functional Genomics and the Biology and Biomedicine (FRIBIO) programs of the Norwegian Research Council [grant number 196898 to T.J.]; and the Norwegian Cancer Society [grant number 71043-PR-2006-0320 to T.J.].

  • Supplementary material available online at

  • Accepted November 15, 2012.
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