Mechanisms of endosomal trafficking in lipid droplet catabolism

脂滴分解代谢中的内体运输机制

基本信息

  • 批准号:
    10714356
  • 负责人:
  • 金额:
    $ 38.19万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-07-15 至 2028-04-30
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Lipids provide a rich source of energy to fuel fundamental cellular processes including migration, differentiation, and survival through periods of low nutrient availability. The storage and utilization of lipid fuel relies on lipid droplets (LD). These unique organelles are surrounded by peripheral phospholipid monolayer that encapsulate a core containing neutral lipids triacylglycerol (TAG) and cholesterol ester (CE). LDs possess a unique proteome of adapters, enzymes, and structural proteins that interact directly with the LD monolayer and regulate trafficking for biogenesis and catabolism. However, detailed mechanistic knowledge regarding the relationship between the LD monolayer and LD trafficking machinery is lacking. This knowledge is especially critical for the process of lipophagy, whereby subpopulations of LDs are selectively targeted for lysosomal degradation. Our preliminary data suggest that LDs possess heterogenous lipid signatures at the level of the LD monolayer, and this heterogeneity influences the fate of certain small LD subpopulations toward lipophagy. Furthermore, we postulate that lipids of the LD monolayer including diacylglycerol (DAG) and phosphatidtyliositol (PI) are modulated by LD catabolic enzymes to influence their trafficking. In Project 1, we will determine the role of adipose triglyceride lipase (ATGL) in generating DAG on the LD surface via TAG hydrolysis, and explore the impact of DAG on the recruitment and activation of protein kinase C (PKC) on the LD surface. In Project 2, we will investigate Rab5 in recruiting PI 3-Kinases to the LD surface to phosphorylate PI, define the role of ESCRT proteins in the trafficking of LDs for lipophagy in mammalian cells. We will also explore an unexpected role for certain ESCRTs in LD biogenesis. The results gained from the proposed research will provide a mechanistic understanding of lipid droplet trafficking and the modulation of the LD monolayer.
项目总结/文摘

项目成果

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Micah Schott其他文献

Micah Schott的其他文献

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{{ truncateString('Micah Schott', 18)}}的其他基金

Mechanisms of lipid droplet trafficking in hepatocellular carcinoma
肝细胞癌中脂滴运输的机制
  • 批准号:
    10644812
  • 财政年份:
    2023
  • 资助金额:
    $ 38.19万
  • 项目类别:
Synergy of lipolysis and lipophagy in alcoholic liver disease
脂肪分解和脂肪吞噬在酒精性肝病中的协同作用
  • 批准号:
    10489818
  • 财政年份:
    2021
  • 资助金额:
    $ 38.19万
  • 项目类别:
Synergy of lipolysis and lipophagy in alcoholic liver disease
脂肪分解和脂肪吞噬在酒精性肝病中的协同作用
  • 批准号:
    10455130
  • 财政年份:
    2021
  • 资助金额:
    $ 38.19万
  • 项目类别:
Synergy of lipolysis and lipophagy in alcoholic liver disease
脂肪分解和脂肪吞噬在酒精性肝病中的协同作用
  • 批准号:
    10686384
  • 财政年份:
    2021
  • 资助金额:
    $ 38.19万
  • 项目类别:
Synergy of lipolysis and lipophagy in alcoholic liver disease
脂肪分解和脂肪吞噬在酒精性肝病中的协同作用
  • 批准号:
    10392064
  • 财政年份:
    2019
  • 资助金额:
    $ 38.19万
  • 项目类别:
Mechanisms of Lipid Heterogeneity in Lipid Droplet Catabolism
脂滴分解代谢中脂质异质性的机制
  • 批准号:
    10714244
  • 财政年份:
    2018
  • 资助金额:
    $ 38.19万
  • 项目类别:

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