Svf1 inhibits reactive oxygen species generation and promotes survival under conditions of oxidative stress in Saccharomyces cerevisiae

Jennifer L. Brace, David J. VanderWeele, Charles M. Rudin

Research output: Contribution to journalArticle

Abstract

Aberrant regulation of apoptosis, or programmed cell death, contributes to the aetiology of several diseases, including cancers, immunodeficiencies and neurodegenerative illnesses. We hypothesized that key features of mammalian cell death regulation maybe conserved in single celled organisms such as the budding yeast Saccharomyces cerevisiae. We previously identified the yeast gene SVF1 in a screen for mutations that could be functionally complemented by exogenous expression of the human anti-apoptotic gene Bcl-xL. Anti-apoptotic Bcl-2 family members have been shown to promote redox stability through upregulation of antioxidant pathways in mammalian cells. Here we demonstrate that the Svf1 protein is required for yeast survival under conditions of oxidative stress, including cold stress. Cells lacking SVF1 are hypersensitive to conditions associated with increased reactive oxygen species (ROS) generation and to direct chemical precursors of ROS, and demonstrate increased levels of ROS under these conditions. Hypersensitivity to oxidative stress can be reversed by treatment with the antioxidant N-acetylcysteine or expression of exogenous SVF1, although exogenous expression of Bcl-xL did not protect cells from cold stress. Exogenous SVF1 expression in mammalian cells confers resistance to H2O2 exposure. Our data are consistent with previous observations suggesting a key role of oxidative stress response in mammalian apoptotic regulation and validate the use of S. cerevisiae as a model for studying programmed cell death.

Original languageEnglish (US)
Pages (from-to)641-652
Number of pages12
JournalYeast
Volume22
Issue number8
DOIs
StatePublished - Jun 2005

Fingerprint

Oxidative stress
Yeast
Saccharomyces cerevisiae
reactive oxygen species
Cell death
Reactive Oxygen Species
Oxidative Stress
oxidative stress
Oxygen
Survival
apoptosis
cold stress
yeasts
Cell Death
Antioxidants
cells
antioxidants
acetylcysteine
Genes
Yeasts

Keywords

  • Apoptosis
  • Bcl-x
  • ROS
  • Yeast

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biotechnology
  • Bioengineering
  • Microbiology

Cite this

Svf1 inhibits reactive oxygen species generation and promotes survival under conditions of oxidative stress in Saccharomyces cerevisiae. / Brace, Jennifer L.; VanderWeele, David J.; Rudin, Charles M.

In: Yeast, Vol. 22, No. 8, 06.2005, p. 641-652.

Research output: Contribution to journalArticle

Brace, Jennifer L. ; VanderWeele, David J. ; Rudin, Charles M. / Svf1 inhibits reactive oxygen species generation and promotes survival under conditions of oxidative stress in Saccharomyces cerevisiae. In: Yeast. 2005 ; Vol. 22, No. 8. pp. 641-652.
@article{b57304387f864a268077fc6e53e0d843,
title = "Svf1 inhibits reactive oxygen species generation and promotes survival under conditions of oxidative stress in Saccharomyces cerevisiae",
abstract = "Aberrant regulation of apoptosis, or programmed cell death, contributes to the aetiology of several diseases, including cancers, immunodeficiencies and neurodegenerative illnesses. We hypothesized that key features of mammalian cell death regulation maybe conserved in single celled organisms such as the budding yeast Saccharomyces cerevisiae. We previously identified the yeast gene SVF1 in a screen for mutations that could be functionally complemented by exogenous expression of the human anti-apoptotic gene Bcl-xL. Anti-apoptotic Bcl-2 family members have been shown to promote redox stability through upregulation of antioxidant pathways in mammalian cells. Here we demonstrate that the Svf1 protein is required for yeast survival under conditions of oxidative stress, including cold stress. Cells lacking SVF1 are hypersensitive to conditions associated with increased reactive oxygen species (ROS) generation and to direct chemical precursors of ROS, and demonstrate increased levels of ROS under these conditions. Hypersensitivity to oxidative stress can be reversed by treatment with the antioxidant N-acetylcysteine or expression of exogenous SVF1, although exogenous expression of Bcl-xL did not protect cells from cold stress. Exogenous SVF1 expression in mammalian cells confers resistance to H2O2 exposure. Our data are consistent with previous observations suggesting a key role of oxidative stress response in mammalian apoptotic regulation and validate the use of S. cerevisiae as a model for studying programmed cell death.",
keywords = "Apoptosis, Bcl-x, ROS, Yeast",
author = "Brace, {Jennifer L.} and VanderWeele, {David J.} and Rudin, {Charles M.}",
year = "2005",
month = "6",
doi = "10.1002/yea.1235",
language = "English (US)",
volume = "22",
pages = "641--652",
journal = "Yeast",
issn = "0749-503X",
publisher = "John Wiley and Sons Ltd",
number = "8",

}

TY - JOUR

T1 - Svf1 inhibits reactive oxygen species generation and promotes survival under conditions of oxidative stress in Saccharomyces cerevisiae

AU - Brace, Jennifer L.

AU - VanderWeele, David J.

AU - Rudin, Charles M.

PY - 2005/6

Y1 - 2005/6

N2 - Aberrant regulation of apoptosis, or programmed cell death, contributes to the aetiology of several diseases, including cancers, immunodeficiencies and neurodegenerative illnesses. We hypothesized that key features of mammalian cell death regulation maybe conserved in single celled organisms such as the budding yeast Saccharomyces cerevisiae. We previously identified the yeast gene SVF1 in a screen for mutations that could be functionally complemented by exogenous expression of the human anti-apoptotic gene Bcl-xL. Anti-apoptotic Bcl-2 family members have been shown to promote redox stability through upregulation of antioxidant pathways in mammalian cells. Here we demonstrate that the Svf1 protein is required for yeast survival under conditions of oxidative stress, including cold stress. Cells lacking SVF1 are hypersensitive to conditions associated with increased reactive oxygen species (ROS) generation and to direct chemical precursors of ROS, and demonstrate increased levels of ROS under these conditions. Hypersensitivity to oxidative stress can be reversed by treatment with the antioxidant N-acetylcysteine or expression of exogenous SVF1, although exogenous expression of Bcl-xL did not protect cells from cold stress. Exogenous SVF1 expression in mammalian cells confers resistance to H2O2 exposure. Our data are consistent with previous observations suggesting a key role of oxidative stress response in mammalian apoptotic regulation and validate the use of S. cerevisiae as a model for studying programmed cell death.

AB - Aberrant regulation of apoptosis, or programmed cell death, contributes to the aetiology of several diseases, including cancers, immunodeficiencies and neurodegenerative illnesses. We hypothesized that key features of mammalian cell death regulation maybe conserved in single celled organisms such as the budding yeast Saccharomyces cerevisiae. We previously identified the yeast gene SVF1 in a screen for mutations that could be functionally complemented by exogenous expression of the human anti-apoptotic gene Bcl-xL. Anti-apoptotic Bcl-2 family members have been shown to promote redox stability through upregulation of antioxidant pathways in mammalian cells. Here we demonstrate that the Svf1 protein is required for yeast survival under conditions of oxidative stress, including cold stress. Cells lacking SVF1 are hypersensitive to conditions associated with increased reactive oxygen species (ROS) generation and to direct chemical precursors of ROS, and demonstrate increased levels of ROS under these conditions. Hypersensitivity to oxidative stress can be reversed by treatment with the antioxidant N-acetylcysteine or expression of exogenous SVF1, although exogenous expression of Bcl-xL did not protect cells from cold stress. Exogenous SVF1 expression in mammalian cells confers resistance to H2O2 exposure. Our data are consistent with previous observations suggesting a key role of oxidative stress response in mammalian apoptotic regulation and validate the use of S. cerevisiae as a model for studying programmed cell death.

KW - Apoptosis

KW - Bcl-x

KW - ROS

KW - Yeast

UR - http://www.scopus.com/inward/record.url?scp=22944455569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22944455569&partnerID=8YFLogxK

U2 - 10.1002/yea.1235

DO - 10.1002/yea.1235

M3 - Article

C2 - 16034825

AN - SCOPUS:22944455569

VL - 22

SP - 641

EP - 652

JO - Yeast

JF - Yeast

SN - 0749-503X

IS - 8

ER -