Journal
JOURNAL OF CELL SCIENCE
Volume 126, Issue 4, Pages 939-952Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.114819
Keywords
Selective autophagy; Pexophagy; Autophagy receptors; NBR1; p62; Peroxisomes
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Funding
- Canadian Institutes of Health Research [MOP-111164]
- Canada Foundation for Innovation [23584]
- Ontario Research Fund [23584]
- Norwegian Research Council [196898]
- Norwegian Cancer Society [71043-PR-2006-0320]
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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 a-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.
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