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Compensatory mechanisms and the type of injury determine the fate of cells with impaired macroautophagy
| Content Provider | Scilit |
|---|---|
| Author | Singh, Rajat Czaja, Mark J. |
| Copyright Year | 2008 |
| Description | Journal: Autophagy 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 up-regulation of chaperone-mediated autophagy. Inhibition of this form of autophagy sensitizes cells to death from menadione, suggesting that the compensatory up-regulation 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. Addendum to: Wang Y, Singh R, Massey AC, Kane SS, Kaushik S, Grant T, Xiang Y, Cuervo AM, Czaja MJ. Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. J Biol Chem 2008; 283:4766-77. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/auto.5800?needAccess=true |
| Ending Page | 518 |
| Page Count | 3 |
| Starting Page | 516 |
| ISSN | 15548627 |
| e-ISSN | 15548635 |
| DOI | 10.4161/auto.5800 |
| Journal | Autophagy |
| Issue Number | 4 |
| Volume Number | 4 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2008-05-16 |
| Access Restriction | Open |
| Subject Keyword | Journal: Autophagy Biochemistry and Molecular Biology Cell Biology Macroautophagy Cellular Death Compensatory |
| Content Type | Text |
| Subject | Cell Biology Molecular Biology |
