Other
12 Authors
- Araki K,
- Behrends C,
- He L,
- Jun Wang Q,
- Friedman SL,
- Lu J,
- Araki M,
- Fiel MI,
- Li M,
- Catanzaro JM,
- Zong WX,
- Yue Z
| First Author | Lu J | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 3920 | PubMed ID | 24849286 |
| Mgi Jnum | J:220500 | Mgi Id | MGI:5634877 |
| Doi | 10.1038/ncomms4920 | Citation | Lu J, et al. (2014) NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity. Nat Commun 5:3920 |
| abstractText | The 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. |
