UM  > 中華醫藥研究院
NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity
Lu J.1; He L.1; Behrends C.6; Araki M.2; Araki K.2; Jun Wang Q.3; Catanzaro J.M.4; Friedman S.L.1; Zong W.-X.4; Fiel M.I.1; Li M.5; Yue Z.1
2014-05-22
Source PublicationNature Communications
ISSN20411723
Volume5
AbstractThe Beclin 1-Vps34 complex, the core component of the class III phosphatidylinositol-3 kinase (PI3K-III), binds Atg14L or UVRAG to control different steps of autophagy. However, the mechanism underlying the control of PI3K-III activity remains elusive. Here we report the identification of NRBF2 as a component in the specific PI3K-III complex and a modulator of PI3K-III activity. Through its microtubule interaction and trafficking (MIT) domain, NRBF2 binds Atg14L directly and enhances Atg14L-linked Vps34 kinase activity and autophagy induction. NRBF2-deficient cells exhibit enhanced vulnerability to endoplasmic reticulum (ER) stress that is reversed by re-introducing exogenous NRBF2. NRBF2-deficient mice develop focal liver necrosis and ductular reaction, accompanied by impaired Atg14L-linked Vps34 activity and autophagy, although the mice show no increased mortality. Our data reveal a key role for NRBF2 in the assembly of the specific Atg14L-Beclin 1-Vps34-Vps15 complex for autophagy induction. Thus, NRBF2 modulates autophagy via regulation of PI3K-III and prevents ER stress-mediated cytotoxicity and liver injury.
DOI10.1038/ncomms4920
URLView the original
Language英語
Fulltext Access
Citation statistics
Cited Times [WOS]:60   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Icahn School of Medicine at Mount Sinai
2.Kumamoto University
3.University of Kentucky
4.Stony Brook University
5.Hong Kong Baptist University
6.Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main
Recommended Citation
GB/T 7714
Lu J.,He L.,Behrends C.,et al. NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity[J]. Nature Communications,2014,5.
APA Lu J..,He L..,Behrends C..,Araki M..,Araki K..,...&Yue Z..(2014).NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity.Nature Communications,5.
MLA Lu J.,et al."NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity".Nature Communications 5(2014).
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Lu J.]'s Articles
[He L.]'s Articles
[Behrends C.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Lu J.]'s Articles
[He L.]'s Articles
[Behrends C.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Lu J.]'s Articles
[He L.]'s Articles
[Behrends C.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.