# Mechanisms of endosomal trafficking in lipid droplet catabolism

> **NIH NIH R35** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $381,931

## Abstract

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.

## Key facts

- **NIH application ID:** 10888296
- **Project number:** 5R35GM150801-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Micah Schott
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $381,931
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888296

## Citation

> US National Institutes of Health, RePORTER application 10888296, Mechanisms of endosomal trafficking in lipid droplet catabolism (5R35GM150801-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10888296. Licensed CC0.

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