Document Detail

Autophagy provides nutrients but can lead to Chop-dependent induction of Bim to sensitize growth factor-deprived cells to apoptosis.
MedLine Citation:
PMID:  19109422     Owner:  NLM     Status:  MEDLINE    
Tissue homeostasis is controlled by the availability of growth factors, which sustain exogenous nutrient uptake and prevent apoptosis. Although autophagy can provide an alternate intracellular nutrient source to support essential basal metabolism of apoptosis-resistant growth factor-withdrawn cells, antiapoptotic Bcl-2 family proteins can suppress autophagy in some settings. Thus, the role of autophagy and interactions between autophagy and apoptosis in growth factor-withdrawn cells expressing Bcl-2 or Bcl-xL were unclear. Here we show autophagy was rapidly induced in hematopoietic cells upon growth factor withdrawal regardless of Bcl-2 or Bcl-xL expression and led to increased mitochondrial lipid oxidation. Deficiency in autophagy-essential gene expression, however, did not lead to metabolic catastrophe and rapid death of growth factor-deprived cells. Rather, inhibition of autophagy enhanced survival of cells with moderate Bcl-2 expression for greater than 1 wk, indicating that autophagy promoted cell death in this time frame. Cell death was not autophagic, but apoptotic, and relied on Chop-dependent induction of the proapoptotic Bcl-2 family protein Bim. Therefore, although ultimately important, autophagy-derived nutrients appear initially nonessential after growth factor withdrawal. Instead, autophagy promotes tissue homeostasis by sensitizing cells to apoptosis to ensure only the most apoptosis-resistant cells survive long-term using autophagy-derived nutrients when growth factor deprived.
Brian J Altman; Jessica A Wofford; Yuxing Zhao; Jonathan L Coloff; Emily C Ferguson; Heather L Wieman; Amanda E Day; Olga Ilkayeva; Jeffrey C Rathmell
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-12-24
Journal Detail:
Title:  Molecular biology of the cell     Volume:  20     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-16     Completed Date:  2009-04-13     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1180-91     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apoptosis Regulatory Proteins / metabolism*
Fatty Acids / metabolism
Glucose / metabolism
Intercellular Signaling Peptides and Proteins / deficiency*
Membrane Proteins / metabolism*
Proto-Oncogene Proteins / metabolism*
Transcription Factor CHOP / metabolism*
bcl-X Protein / metabolism
Grant Support
R01 CA123350/CA/NCI NIH HHS; R01 CA123350/CA/NCI NIH HHS; R01 CA123350-03/CA/NCI NIH HHS
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/Fatty Acids; 0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/bcl-X Protein; 147336-12-7/Transcription Factor CHOP; IY9XDZ35W2/Glucose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  GM130-dependent control of Cdc42 activity at the Golgi regulates centrosome organization.
Next Document:  The anaphase-promoting complex promotes actomyosin-ring disassembly during cytokinesis in yeast.