Compensatory mechanisms and the type of injury determine the fate of cells with impaired macroautophagy

Rajat Singh, Mark J. Czaja

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 macroautophagy. 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-α. 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.

Original languageEnglish (US)
Pages (from-to)516-518
Number of pages3
JournalAutophagy
Volume4
Issue number4
DOIs
StatePublished - May 16 2008

Keywords

  • Apoptosis
  • Chaperone-mediated autophagy
  • Fas
  • Menadione
  • Tumor necrosis factor-α; oxidative stress
  • UV light

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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