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Regulation of the PAH1-encoded phosphatidate phosphatase and its role in lipid metabolism in yeast

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TitleInfo
Title
Regulation of the PAH1-encoded phosphatidate phosphatase and its role in lipid metabolism in yeast
Name (type = personal)
NamePart (type = family)
Pascual
NamePart (type = given)
Florencia
DisplayForm
Florencia Pascual
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Carman
NamePart (type = given)
George M.
DisplayForm
George M. Carman
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Chikindas
NamePart (type = given)
Michael
DisplayForm
Michael Chikindas
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Han
NamePart (type = given)
Gil-Soo
DisplayForm
Gil-Soo Han
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Quadro
NamePart (type = given)
Loredana
DisplayForm
Loredana Quadro
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Storch
NamePart (type = given)
Judith
DisplayForm
Judith Storch
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2013
DateOther (qualifier = exact); (type = degree)
2013-10
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
The yeast PAH1-encoded phosphatidate phosphatase (PAP) catalyzes the penultimate step in the synthesis of triacylglycerol (TAG). PAP plays a crucial role in lipid homeostasis by controlling the relative proportions of its substrate phosphatidate (PA) and its product diacylglycerol (DAG). The cellular amounts of these lipid intermediates influence the synthesis of TAG and the pathways by which membrane phospholipids are synthesized. The importance of this enzyme is exemplified by the severe phenotypes of the pah1 mutant that include deregulation of phospholipid synthesis, an aberrant expansion of the nuclear/ER membrane, a decrease in lipid droplet formation, a massive reduction in TAG content, defects in vacuole homeostasis and fusion, and increased sensitivity to lipotoxicity. On the other hand, the attenuation of PAH1-encoded PAP function is also essential to normal cell physiology. Indeed, the overexpression of an unregulated form of PA phosphatase inhibits cell growth, and this is attributed to the depletion of PA needed for phospholipid synthesis via CDP-DAG and the accumulation of DAG to a toxic level. TAG accumulates in the stationary phase of growth, and the lipid analysis of the pah1 mutant established the essential role of Pah1p PAP in this process. While Pah1p PAP activity was elevated in stationary phase cells, the expression of PAH1 mRNA and Pah1p was maximal in the exponential phase, but declined as cells entered the stationary phase. The levels of Pah1p were stabilized in stationary phase cells treated with the proteasome inhibitor MG132 as well as in several mutants that exhibit a decrease in proteasome function. Catalytic site mutant forms of Pah1p exhibited increased stability in stationary phase, indicating that the balance of PA and DAG acts as a signal for the degradation of the enzyme. Additionally, Pah1p levels were also stabilized in cells overexpressing DGK1, pointing to PA as a possible regulator of Pah1p stability. This work reveals a novel mechanism for the control of Pah1p PAP function in yeast.
Subject (authority = RUETD)
Topic
Food Science
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_4913
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xiv, 181 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Florencia Pascual
Subject (authority = ETD-LCSH)
Topic
Yeast
Subject (authority = ETD-LCSH)
Topic
Phosphatidate phosphatase
Subject (authority = ETD-LCSH)
Topic
Lipids--Metabolism
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3862DGN
Genre (authority = ExL-Esploro)
ETD doctoral
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RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Pascual
GivenName
Florencia
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2013-07-18 18:28:19
AssociatedEntity
Name
Florencia Pascual
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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