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Role of Lipid Transfer Proteins in Lipid Droplet Dynamics
Role of Lipid Transfer Proteins in Lipid Droplet Dynamics
Role of Lipid Transfer Proteins in Lipid Droplet Dynamics

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211150947
ISBN  
9798383567067
DDC  
574
저자명  
Wan, Neng.
서명/저자  
Role of Lipid Transfer Proteins in Lipid Droplet Dynamics
발행사항  
[Sl] : Yale University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
107 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-02, Section: B.
주기사항  
Advisor: Reinisch, Karin M.
학위논문주기  
Thesis (Ph.D.)--Yale University, 2024.
초록/해제  
요약Eukaryotic cells compartmentalize their cellular processes in organelles. Lipid droplets (LDs) are key organellesin energy and membrane lipid homeostasis. It has become evident that LDs form membrane contact sites with other organelles throughout their lifetime, from biogenesis to degradation. Lipid transfer proteins (LTPs) localize to LDs, often at sites of LD-organelle contacts. Several known and newly identified LTPs impact LDs biogenesis and degradation, suggesting a role of protein mediated lipid transport in modulating LDs dynamics. The mechanisms of how lipid transport precisely participates in these functions is largely unclear. I characterized the protein spartin, mutations of which leads to neurological disease Troyer syndrome. Spartin localizes to LDs and participates in lipophagy to degrade LDs by tethering LDs close to autophagosome. We hypothesized that spartin might possess lipid transfer activity, like other protein tethers at membrane contact sites. Using biochemical and structural approaches, I discovered that spartin copurifies with phospholipids and neutral lipids from cells and transfers phospholipids in vitro via a so-called senescence domain. A senescence domain truncation impairs lipid transfer in vitro and also impairs LD turnover in cells while not affecting spartin's association with either LDs or autophagosomes, supporting that spartin's lipid transfer ability is physiologically relevant. In summary, my data indicates a novel function of protein mediated lipid transfer in LD degradation, including by lipophagy.
일반주제명  
Cellular biology
일반주제명  
Molecular biology
일반주제명  
Biochemistry
일반주제명  
Genetics
키워드  
Lipid droplets
키워드  
Lipid trafficking
키워드  
Lipid transfer proteins
키워드  
Lipophagy
키워드  
Eukaryotic cells
기타저자  
Yale University Cell Biology
기본자료저록  
Dissertations Abstracts International. 86-02B.
전자적 위치 및 접속  
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■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a574
■1001  ▼aWan,  Neng.
■24510▼aRole  of  Lipid  Transfer  Proteins  in  Lipid  Droplet  Dynamics
■260    ▼a[Sl]▼bYale  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a107  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-02,  Section:  B.
■500    ▼aAdvisor:  Reinisch,  Karin  M.
■5021  ▼aThesis  (Ph.D.)--Yale  University,  2024.
■520    ▼aEukaryotic  cells  compartmentalize  their  cellular  processes  in  organelles.  Lipid  droplets  (LDs)  are  key  organellesin  energy  and  membrane  lipid  homeostasis.  It  has  become  evident  that  LDs  form  membrane  contact  sites  with  other  organelles  throughout  their  lifetime,  from  biogenesis  to  degradation.  Lipid  transfer  proteins  (LTPs)  localize  to  LDs,  often  at  sites  of  LD-organelle  contacts.  Several  known  and  newly  identified  LTPs  impact  LDs  biogenesis  and  degradation,  suggesting  a  role  of  protein  mediated  lipid  transport  in  modulating  LDs  dynamics.  The  mechanisms  of  how  lipid  transport  precisely  participates  in  these  functions  is  largely  unclear. I  characterized  the  protein  spartin,  mutations  of  which  leads  to  neurological  disease  Troyer  syndrome.  Spartin  localizes  to  LDs  and  participates  in  lipophagy  to  degrade  LDs  by  tethering  LDs  close  to  autophagosome.  We  hypothesized  that  spartin  might  possess  lipid  transfer  activity,  like  other  protein  tethers  at  membrane  contact  sites.  Using  biochemical  and  structural  approaches,  I  discovered  that  spartin  copurifies  with  phospholipids  and  neutral  lipids  from  cells  and  transfers  phospholipids  in  vitro  via  a  so-called  senescence  domain.  A  senescence  domain  truncation  impairs  lipid  transfer  in  vitro  and  also  impairs  LD  turnover  in  cells  while  not  affecting  spartin's  association  with  either  LDs  or  autophagosomes,  supporting  that  spartin's  lipid  transfer  ability  is  physiologically  relevant.  In  summary,  my  data  indicates  a  novel  function  of  protein  mediated  lipid  transfer  in  LD  degradation,  including  by  lipophagy.
■590    ▼aSchool  code:  0265.
■650  4▼aCellular  biology
■650  4▼aMolecular  biology
■650  4▼aBiochemistry
■650  4▼aGenetics
■653    ▼aLipid  droplets
■653    ▼aLipid  trafficking
■653    ▼aLipid  transfer  proteins
■653    ▼aLipophagy
■653    ▼aEukaryotic  cells
■690    ▼a0379
■690    ▼a0487
■690    ▼a0369
■690    ▼a0307
■71020▼aYale  University▼bCell  Biology.
■7730  ▼tDissertations  Abstracts  International▼g86-02B.
■790    ▼a0265
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160273▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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