PMID- 21926971
OWN - NLM
STAT- MEDLINE
DCOM- 20120105
LR  - 20230815
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 30
IP  - 21
DP  - 2011 Sep 16
TI  - BAX inhibitor-1 regulates autophagy by controlling the IRE1alpha branch of the 
      unfolded protein response.
PG  - 4465-78
LID - 10.1038/emboj.2011.318 [doi]
AB  - 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.
FAU - Castillo, Karen
AU  - Castillo K
AD  - Center for Molecular Studies of the Cell, Department of Cellular and Molecular 
      Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
FAU - Rojas-Rivera, Diego
AU  - Rojas-Rivera D
FAU - Lisbona, Fernanda
AU  - Lisbona F
FAU - Caballero, Benjamin
AU  - Caballero B
FAU - Nassif, Melissa
AU  - Nassif M
FAU - Court, Felipe A
AU  - Court FA
FAU - Schuck, Sebastian
AU  - Schuck S
FAU - Ibar, Consuelo
AU  - Ibar C
FAU - Walter, Peter
AU  - Walter P
FAU - Sierralta, Jimena
AU  - Sierralta J
FAU - Glavic, Alvaro
AU  - Glavic A
FAU - Hetz, Claudio
AU  - Hetz C
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110916
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Acids)
RN  - 0 (Membrane Proteins)
RN  - 0 (Tmbim6 protein, mouse)
RN  - EC 2.7.11.1 (Ern1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.- (Endoribonucleases)
SB  - IM
EIN - EMBO J. 2017 Jun 1;36(11):1640. PMID: 28572284
EIN - EMBO J. 2021 Nov 2;40(21):e109149. PMID: 34726286
MH  - Acids/metabolism
MH  - Animals
MH  - Autophagy/*genetics
MH  - Cell Survival/genetics
MH  - Cells, Cultured
MH  - Drosophila/genetics
MH  - Endoribonucleases/*metabolism/physiology
MH  - Membrane Proteins/genetics/metabolism/*physiology
MH  - Mice
MH  - Organisms, Genetically Modified
MH  - Phagosomes/genetics/metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism/physiology
MH  - Saccharomyces cerevisiae/genetics
MH  - Signal Transduction/genetics/physiology
MH  - Starvation/metabolism
MH  - Transport Vesicles/metabolism
MH  - Unfolded Protein Response/*genetics/physiology
PMC - PMC3230375
COIS- The authors declare that they have no conflict of interest.
EDAT- 2011/09/20 06:00
MHDA- 2012/01/06 06:00
PMCR- 2012/11/02
CRDT- 2011/09/20 06:00
PHST- 2011/01/31 00:00 [received]
PHST- 2011/08/01 00:00 [accepted]
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/01/06 06:00 [medline]
PHST- 2012/11/02 00:00 [pmc-release]
AID - emboj2011318 [pii]
AID - 10.1038/emboj.2011.318 [doi]
PST - epublish
SO  - EMBO J. 2011 Sep 16;30(21):4465-78. doi: 10.1038/emboj.2011.318.