| First Author | Castillo K | Year | 2011 |
| Journal | EMBO J | Volume | 30 |
| Issue | 21 | Pages | 4465-78 |
| PubMed ID | 21926971 | Mgi Jnum | J:180014 |
| Mgi Id | MGI:5304992 | Doi | 10.1038/emboj.2011.318 |
| Citation | Castillo K, et al. (2011) BAX inhibitor-1 regulates autophagy by controlling the IRE1alpha branch of the unfolded protein response. EMBO J 30(21):4465-78 |
| abstractText | Both autophagy and apoptosis are tightly regulated processes playing a central role in tissue homeostasis. Bax inhibitor 1 (BI-1) is a highly conserved protein with a dual role in apoptosis and endoplasmic reticulum (ER) stress signalling through the regulation of the ER stress sensor inositol requiring kinase 1 alpha (IRE1alpha). Here, we describe a novel function of BI-1 in the modulation of autophagy. BI-1-deficient cells presented a faster and stronger induction of autophagy, increasing LC3 flux and autophagosome formation. These effects were associated with enhanced cell survival under nutrient deprivation. Repression of autophagy by BI-1 was dependent on cJun-N terminal kinase (JNK) and IRE1alpha expression, possibly due to a displacement of TNF-receptor associated factor-2 (TRAF2) from IRE1alpha. Targeting BI-1 expression in flies altered autophagy fluxes and salivary gland degradation. BI-1 deficiency increased flies survival under fasting conditions. Increased expression of autophagy indicators was observed in the liver and kidney of bi-1-deficient mice. In summary, we identify a novel function of BI-1 in multicellular organisms, and suggest a critical role of BI-1 as a stress integrator that modulates autophagy levels and other interconnected homeostatic processes. |
