Document Detail

Autophagy and phagocytosis-like cell cannibalism exert opposing effects on cellular survival during metabolic stress.
MedLine Citation:
PMID:  22498699     Owner:  NLM     Status:  MEDLINE    
Understanding mechanisms controlling neuronal cell death and survival under conditions of altered energy supply (e.g., during stroke) is fundamentally important for the development of therapeutic strategies. The function of autophagy herein is unclear, as both its beneficial and detrimental roles have been described. We previously demonstrated that loss of AMP-activated protein kinase (AMPK), an evolutionarily conserved enzyme that maintains cellular energy balance, leads to activity-dependent degeneration in neuronal tissue. Here, we show that energy depletion in Drosophila AMPK mutants results in increased autophagy that convincingly promotes, rather than rescues, neurodegeneration. The generated excessive autophagic response is accompanied by increased TOR and S6K activity in the absence of an AMPK-mediated negative regulatory feedback loop. Moreover, energy-depleted neurons use a phagocytic-like process as a means to cellular survival at the expense of surrounding cells. Consequently, phagocytosis stimulation by expression of the scavenger receptor Croquemort significantly delays neurodegeneration. This study thus reveals a potentially novel strategy for cellular survival during conditions of extreme energy depletion, resembling xeno-cannibalistic events seen in metastatic tumors. We provide new insights into the roles of autophagy and phagocytosis in the neuronal metabolic stress response and open new avenues into understanding of human disease and development of therapeutic strategies.
J Poels; M R Spasić; M Gistelinck; J Mutert; A Schellens; P Callaerts; K K Norga
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-13
Journal Detail:
Title:  Cell death and differentiation     Volume:  19     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-10     Completed Date:  2013-01-14     Revised Date:  2013-10-13    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  1590-601     Citation Subset:  IM    
Laboratory of Behavioral and Developmental Genetics, Leuven, Belgium.
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MeSH Terms
AMP-Activated Protein Kinases / deficiency,  genetics,  metabolism*
Autophagy / drug effects*
Cytophagocytosis / drug effects*
Drosophila / enzymology
Drosophila Proteins / genetics,  metabolism
Energy Metabolism
Lithium Chloride / pharmacology*
Neurons / cytology,  metabolism
Ribosomal Protein S6 Kinases / metabolism
TOR Serine-Threonine Kinases / metabolism
Reg. No./Substance:
0/Drosophila Proteins; 7447-41-8/Lithium Chloride; EC Serine-Threonine Kinases; EC Protein Kinases; EC Protein S6 Kinases

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