NBR1 acts as an autophagy receptor for peroxisomes
NBR1 acts as an autophagy receptor for peroxisomes
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DOI：
10.1242/jcs.114819
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发表时间：
2013-02-15
影响因子：
4
通讯作者：
Kim, Peter K.
中科院分区：
文献类型：
--
作者：
Deosaran, Elizabeth;Larsen, Kenneth B.;Kim, Peter K.
选择性巨噬是一种胞内过程，大的细胞质物质在溶酶体中被选择性地隔离和降解。底物选择是通过泛素化和募集泛素结合的自噬受体如p62、NBR1、NDP52和Optineurin来调节的。尽管已经证明这些受体协同作用于某些类型的底物，以新生自噬小体为靶标，但它们的确切作用还没有被很好地理解。我们研究了过氧化物体的选择性自噬降解(附噬作用)，发现NBR1是附噬作用的必要条件和充分条件。NBR1的诱变研究表明，两亲性α-螺旋J结构域、泛素相关(UBA)结构域、Lc3-相互作用区域和盘绕线圈结构域是介导吞噬作用所必需的。值得注意的是，底物选择性部分是由NBR1本身通过J和UBA结构域与过氧化物酶体的一致结合实现的。虽然当NBR1过量时，p62不是必需的，但它与NBR1的结合提高了NBR1介导的吞噬效率。综上所述，这些结果表明NBR1是自噬的特异性受体。
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.