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Vacuolar H+-ATPase (V-ATPase) Promotes Vacuolar Membrane Permeabilization and Nonapoptotic Death in Stressed Yeast.

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Title: Vacuolar H+-ATPase (V-ATPase) Promotes Vacuolar Membrane Permeabilization and Nonapoptotic Death in Stressed Yeast.
Authors: Kim, Hyemin1, Kim, Adam1, Cunningham, Kyle W.1 kwc@jhu.edu.
Source: Journal of Biological Chemistry. 6/1/2012, Vol. 287 Issue 23, p19029-19039. 11p.
Subjects: Yeast, Cell death, Cells, Death (Biology), Protein kinases, Phosphotransferases
Abstract: Stress in the endoplasmic reticulum caused by tunicamycin, dithiothreitol, and azole-class antifungal drugs can induce nonapoptotic cell death in yeasts that can be blocked by the action of calcineurin (Cn), a Ca2+-dependent serine/threonine protein phosphatase. To identify additional factors that regulate nonapoptotic cell death in yeast, a collection of gene knock-out mutants was screened for mutants exhibiting altered survival rates. The screen revealed an endocytic protein (Ede1) that can function upstream of Ca2+/calmodulin-dependent protein kinase 2 (Cmk2) to suppress cell death in parallel to Cn. The screen also revealed the vacuolar H+-ATPase (V-ATPase), which acidifies the lysosome-like vacuole. The V-ATPase performed its death-promoting functions very soon after imposition of the stress and was not required for later stages of the cell death program. Cn did not inhibit V-ATPase activities but did block vacuole membrane permeabilization (VMP), which occurred at late stages of the cell death program. All of the other nondying mutants identified in the screens blocked steps before VMP. These findings suggest that VMP is the lethal event in dying yeast cells and that fungi may employ a mechanism of cell death similar to the necrosis-like cell death of degenerating neurons. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Vacuolar H<superscript>+</superscript>-ATPase (V-ATPase) Promotes Vacuolar Membrane Permeabilization and Nonapoptotic Death in Stressed Yeast.
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  Data: <searchLink fieldCode="AR" term="%22Kim%2C+Hyemin%22">Kim, Hyemin</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Kim%2C+Adam%22">Kim, Adam</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Cunningham%2C+Kyle+W%2E%22">Cunningham, Kyle W.</searchLink><relatesTo>1</relatesTo><i> kwc@jhu.edu.</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 6/1/2012, Vol. 287 Issue 23, p19029-19039. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Yeast%22">Yeast</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+death%22">Cell death</searchLink><br /><searchLink fieldCode="DE" term="%22Cells%22">Cells</searchLink><br /><searchLink fieldCode="DE" term="%22Death+%28Biology%29%22">Death (Biology)</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+kinases%22">Protein kinases</searchLink><br /><searchLink fieldCode="DE" term="%22Phosphotransferases%22">Phosphotransferases</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Stress in the endoplasmic reticulum caused by tunicamycin, dithiothreitol, and azole-class antifungal drugs can induce nonapoptotic cell death in yeasts that can be blocked by the action of calcineurin (Cn), a Ca2+-dependent serine/threonine protein phosphatase. To identify additional factors that regulate nonapoptotic cell death in yeast, a collection of gene knock-out mutants was screened for mutants exhibiting altered survival rates. The screen revealed an endocytic protein (Ede1) that can function upstream of Ca2+/calmodulin-dependent protein kinase 2 (Cmk2) to suppress cell death in parallel to Cn. The screen also revealed the vacuolar H+-ATPase (V-ATPase), which acidifies the lysosome-like vacuole. The V-ATPase performed its death-promoting functions very soon after imposition of the stress and was not required for later stages of the cell death program. Cn did not inhibit V-ATPase activities but did block vacuole membrane permeabilization (VMP), which occurred at late stages of the cell death program. All of the other nondying mutants identified in the screens blocked steps before VMP. These findings suggest that VMP is the lethal event in dying yeast cells and that fungi may employ a mechanism of cell death similar to the necrosis-like cell death of degenerating neurons. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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    Identifiers:
      – Type: doi
        Value: 10.1074/jbc.M112.363390
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 11
        StartPage: 19029
    Subjects:
      – SubjectFull: Yeast
        Type: general
      – SubjectFull: Cell death
        Type: general
      – SubjectFull: Cells
        Type: general
      – SubjectFull: Death (Biology)
        Type: general
      – SubjectFull: Protein kinases
        Type: general
      – SubjectFull: Phosphotransferases
        Type: general
    Titles:
      – TitleFull: Vacuolar H+-ATPase (V-ATPase) Promotes Vacuolar Membrane Permeabilization and Nonapoptotic Death in Stressed Yeast.
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            NameFull: Kim, Hyemin
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            NameFull: Kim, Adam
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            NameFull: Cunningham, Kyle W.
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            – D: 01
              M: 06
              Text: 6/1/2012
              Type: published
              Y: 2012
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              Value: 287
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              Value: 23
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            – TitleFull: Journal of Biological Chemistry
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