Old yellow enzymes, highly homologous FMN oxidoreductases with modulating roles in oxidative stress and programmed cell death in yeast
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Old yellow enzymes, highly homologous FMN oxidoreductases with modulating roles in oxidative stress and programmed cell death in yeast. / Odat, Osama; Matta, Samer; Khalil, Hadi; Kampranis, Sotirios; Pfau, Raymond; Tsichlis, Philip N; Makris, Antonios M.
In: The Journal of Biological Chemistry, Vol. 282, No. 49, 07.12.2007, p. 36010-23.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Old yellow enzymes, highly homologous FMN oxidoreductases with modulating roles in oxidative stress and programmed cell death in yeast
AU - Odat, Osama
AU - Matta, Samer
AU - Khalil, Hadi
AU - Kampranis, Sotirios
AU - Pfau, Raymond
AU - Tsichlis, Philip N
AU - Makris, Antonios M
PY - 2007/12/7
Y1 - 2007/12/7
N2 - In a genetic screen to identify modifiers of Bax-dependent lethality in yeast, the C terminus of OYE2 was isolated based on its capacity to restore sensitivity to a Bax-resistant yeast mutant strain. Overexpression of full-length OYE2 suppresses Bax lethality in yeast, lowers endogenous reactive oxygen species (ROS), increases resistance to H(2)O(2)-induced programmed cell death (PCD), and significantly lowers ROS levels generated by organic prooxidants. Reciprocally, Delta oye2 yeast strains are sensitive to prooxidant-induced PCD. Overexpression and knock-out analysis indicate these OYE2 antioxidant activities are opposed by OYE3, a highly homologous heterodimerizing protein, which functions as a prooxidant promoting H(2)O(2)-induced PCD in wild type yeast. To exert its effect OYE3 requires the presence of OYE2. Deletion of the 12 C-terminal amino acids and catalytic inactivation of OYE2 by a Y197F mutation enhance significantly survival upon H(2)O(2)-induced PCD in wild type cells, but accelerate PCD in Delta oye3 cells, implicating the oye2p-oye3p heterodimer for promoting cell death upon oxidative stress. Unexpectedly, a strain with a double knock-out of these genes (Delta oye2 oye3) is highly resistant to H(2)O(2)-induced PCD, exhibits increased respiratory capacity, and undergoes less cell death during the adaptive response in chronological aging. Simultaneous deletion of OYE2 and other antioxidant genes hyperinduces endogenous levels of ROS, promoting H(2)O(2)-induced cell death: in Delta oye2 glr1 yeast high levels of oxidized glutathione elicited gross morphological aberrations involving the actin cytoskeleton and defects in organelle partitioning. Altering the ratio of reduced to oxidized glutathione by exogenous addition of GSH fully reversed these alterations. Based on this work, OYE proteins are firmly placed in the signaling network connecting ROS generation, PCD modulation, and cytoskeletal dynamics in yeast.
AB - In a genetic screen to identify modifiers of Bax-dependent lethality in yeast, the C terminus of OYE2 was isolated based on its capacity to restore sensitivity to a Bax-resistant yeast mutant strain. Overexpression of full-length OYE2 suppresses Bax lethality in yeast, lowers endogenous reactive oxygen species (ROS), increases resistance to H(2)O(2)-induced programmed cell death (PCD), and significantly lowers ROS levels generated by organic prooxidants. Reciprocally, Delta oye2 yeast strains are sensitive to prooxidant-induced PCD. Overexpression and knock-out analysis indicate these OYE2 antioxidant activities are opposed by OYE3, a highly homologous heterodimerizing protein, which functions as a prooxidant promoting H(2)O(2)-induced PCD in wild type yeast. To exert its effect OYE3 requires the presence of OYE2. Deletion of the 12 C-terminal amino acids and catalytic inactivation of OYE2 by a Y197F mutation enhance significantly survival upon H(2)O(2)-induced PCD in wild type cells, but accelerate PCD in Delta oye3 cells, implicating the oye2p-oye3p heterodimer for promoting cell death upon oxidative stress. Unexpectedly, a strain with a double knock-out of these genes (Delta oye2 oye3) is highly resistant to H(2)O(2)-induced PCD, exhibits increased respiratory capacity, and undergoes less cell death during the adaptive response in chronological aging. Simultaneous deletion of OYE2 and other antioxidant genes hyperinduces endogenous levels of ROS, promoting H(2)O(2)-induced cell death: in Delta oye2 glr1 yeast high levels of oxidized glutathione elicited gross morphological aberrations involving the actin cytoskeleton and defects in organelle partitioning. Altering the ratio of reduced to oxidized glutathione by exogenous addition of GSH fully reversed these alterations. Based on this work, OYE proteins are firmly placed in the signaling network connecting ROS generation, PCD modulation, and cytoskeletal dynamics in yeast.
KW - Actins
KW - Amino Acid Sequence
KW - Amino Acid Substitution
KW - Apoptosis
KW - Cytoskeleton
KW - FMN Reductase
KW - Glutathione
KW - Hydrogen Peroxide
KW - Mutation, Missense
KW - Oxidants
KW - Oxidation-Reduction
KW - Oxidative Stress
KW - Oxygen Consumption
KW - Reactive Oxygen Species
KW - Saccharomyces cerevisiae
KW - Saccharomyces cerevisiae Proteins
KW - Sequence Deletion
KW - bcl-2-Associated X Protein
U2 - 10.1074/jbc.M704058200
DO - 10.1074/jbc.M704058200
M3 - Journal article
C2 - 17897954
VL - 282
SP - 36010
EP - 36023
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 49
ER -
ID: 159085155