Journal
AUTOPHAGY
Volume 4, Issue 4, Pages 516-518Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.5800
Keywords
apoptosis; Fas; tumor necrosis factor-alpha; oxidative stress; menadione; UV light; chaperone-mediated autophagy
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Funding
- NIDDK NIH HHS [R01 DK044234, R01 DK061498, DK044234] Funding Source: Medline
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The relationship between the degradative process of autophagy and cellular death pathways remains unclear. Macroautophagy may potentially function to prevent or promote cell death, and both effects have been reported in studies of cells with a block in macro-autophagy. To better delineate the function of macroautophagy in cell death, we contrasted the responses to death stimuli in wild-type and atg5(-/-) murine embryonic fibroblasts. We have reported that a knockout of the critical macroautophagy gene ATG5 sensitizes cells to death receptor ligand-induced death from Fas and tumor necrosis factor-m Death occurs by caspase-dependent apoptosis resulting from activation of the mitochondrial death pathway. In contrast, atg5(-/-) cells are more resistant to death induced by oxidative stress from menadione or UV light. This resistance was associated with an upregulation of chaperone-mediated autophagy, Inhibition of this form of autophagy sensitizes cells to death from menadione, suggesting that the compensatory upregulation of chaperone-mediated autophagy, and not the loss of macroautophagy, prevents death from menadione. These findings demonstrate that the effects of a loss of macroautophagy on the cellular death response differ depending on the mechanism of cellular injury and the compensatory changes in other forms of autophagy.
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