Document Detail

SLC33A1/AT-1 protein regulates the induction of autophagy downstream of IRE1/XBP1 pathway.
MedLine Citation:
PMID:  22787145     Owner:  NLM     Status:  MEDLINE    
One of the main functions of the unfolded protein response is to ensure disposal of large protein aggregates that accumulate in the lumen of the endoplasmic reticulum (ER) whereas avoiding, at least under nonlethal levels of ER stress, cell death. When tightly controlled, autophagy-dependent ER-associated degradation (ERAD(II)) allows the cell to recover from the transient accumulation of protein aggregates; however, when unchecked, it can be detrimental and cause autophagic cell death/type 2 cell death. Here we show that IRE1/XBP1 controls the induction of autophagy/ERAD(II) during the unfolded protein response by activating the ER membrane transporter SLC33A1/AT-1, which ensures continuous supply of acetyl-CoA into the lumen of the ER. Failure to induce AT-1 leads to widespread autophagic cell death. Mechanistically, the regulation of the autophagic process involves N(ε)-lysine acetylation of Atg9A.
Mariana Pehar; Mary Cabell Jonas; Theresa M Hare; Luigi Puglielli
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-27     Completed Date:  2012-11-19     Revised Date:  2013-08-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29921-30     Citation Subset:  IM    
Department of Medicine, University of Wisconsin, Madison, WI 53705, USA.
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MeSH Terms
Acetyl Coenzyme A / genetics,  metabolism
Autophagy / physiology*
CHO Cells
DNA-Binding Proteins / genetics,  metabolism*
Endoplasmic Reticulum Stress / physiology*
Endoplasmic Reticulum-Associated Degradation / physiology*
Endoribonucleases / genetics,  metabolism*
Membrane Proteins / genetics,  metabolism*
Membrane Transport Proteins / genetics,  metabolism*
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Transcription Factors / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Atg9a protein, human; 0/DNA-Binding Proteins; 0/Membrane Proteins; 0/Membrane Transport Proteins; 0/SLC33A1 protein, human; 0/Transcription Factors; 0/regulatory factor X transcription factors; 72-89-9/Acetyl Coenzyme A; EC 2.7.1.-/ERN2 protein, human; EC Kinases; EC 3.1.-/Endoribonucleases

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