Identification of autophagy genes participating in zinc-induced necrotic cell death in<i>Saccharomyces cerevisiae</i>

Dziedzic, Slawomir A.; Caplan, Allan

doi:10.4161/auto.7.5.14872

Cited by 17 publications

(22 citation statements)

References 62 publications

(68 reference statements)

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“…Previous studies showed that autophagic mutants displayed one of three different phenotypes when grown on excess zinc. 13 Some mutants like Datg29 had no effect on zinc tolerance. Others like Datg8 were more resistant to zinc than the parental strain, while a handful like Datg11 were more sensitive.…”

Section: Resultsmentioning

confidence: 99%

“…27 In contrast, the life-extending process that was activated during leucine starvation to prevent PI accumulation depended on Atg11 suggesting that this type of autophagy operated selectively, 29 like the one that protected cells from excess zinc. 13 Also like zincstressed cells, leucine-starved ones appeared to simultaneously carry out a death-promoting process, although in this case, one dependent not only on Atg8, but also on Atg29. Both proteins are considered vital for macroautophagy.…”

Section: +mentioning

confidence: 99%

“…Previous studies reported that zinc-treated cells predominantly died through necrosis, based on PI accumulation, on their failure to bind annexin V, and on the fact that survival was not affected by the loss of any one of four genes involved in apoptosis. 13 Even before the colony-forming ability of the population of nitrogen-starved cells began to decline (Fig. 1A), the percentage of PI-accumulating cells began to increase (Fig.…”

Section: +mentioning

confidence: 99%

“…12 A study using yeast recently presented evidence for just such a case. 13 Cells treated with 13 mM Zn 2+ died necrotically unless any one of seven autophagy genes was inactivated. At the same time, inactivation of other autophagy genes accelerated cell death, while the inactivation of the remaining genes had no effect on survival at all.…”

Section: Introductionmentioning

confidence: 99%

“…17 In at least one study, inhibiting the mouse equivalents of the yeast genes ATG7 and ATG8 blocked autophagic harvesting of catalase, and by doing so, prevented necrotic death resulting from a catastrophic increase in reactive oxygen-caused damage. 18 The contribution of autophagy to zinc-induced necrotic cell death (ziNCD) in yeast 13 might therefore not be as unusual as it first seems, but merely an extreme example of the cell's response to a number of lethal treatments.…”

Section: Introductionmentioning

confidence: 99%

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Autophagy proteins play cytoprotective and cytocidal roles in leucine starvation-induced cell death inSaccharomyces cerevisiae

Dziedzic

Caplan

2012

Autophagy

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minimal medium with 2% dextrose and all required nutrients unless indicated; SG, synthetic minimal medium with 2% galactose and all required nutrients unless indicated; YPD, yeast peptone medium with 2% dextrose; ziNCD, zinc-induced necrotic cell deathAutophagy is essential for prolonging yeast survival during nutrient deprivation; however, this report shows that some autophagy proteins may also be accelerating population death in those conditions. While leucine starvation caused YCA1-mediated apoptosis characterized by increased annexin V staining, nitrogen deprivation triggered necrotic death characterized by increased propidium iodide uptake. Although a Datg8 strain died faster than its parental strain during nitrogen starvation, this mutant died slower than its parent during leucine starvation. Conversely, a Datg11 strain died slower than its parent during nitrogen starvation, but faster during leucine starvation. Curiously, although GFP-Atg8 complemented the Datg8 mutation, this protein made ATG8 cells more sensitive to nitrogen starvation, and less sensitive to leucine starvation. These results were difficult to explain if autophagy only extended life but could be an indication that a second form of autophagy could concurrently facilitate either apoptotic or necrotic cell death.

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Section: Resultsmentioning

confidence: 99%