# Mechanism of Lipid Droplet/ Mitochondria Contacts and Role of Perilipin 5 in Lipid Metabolism

> **NIH NIH F32** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $68,562

## Abstract

PROJECT SUMMARY
Fatty acids (FAs) are essential for cellular energy storage and as the precursors for synthesis of many lipids.
FAs are predominantly stored as triglycerides in organelles called lipid droplets (LDs). LDs form dynamic
membrane contacts with other organelles including mitochondria (Mito), a site of FA oxidation. These contacts
are proposed to facilitate the trafficking of lipids between organelles. Impaired FA trafficking and metabolism
can lead to a variety of serious diseases. Lipodystrophy and cachexia are caused by deficient lipid storage,
while the metabolic syndrome, type 2 diabetes, atherosclerosis and fatty liver disease involve excess lipid
storage. Therefore, there is a critical need to identify the mechanism and physiological functions of LD-
organelle contacts. Perilipin 5 (Plin5) is an LD protein that mediates LD-Mito contacts. The overall objectives
are to (i) identify the mechanism by which Plin5 induces LD-Mito contacts (ii), to determine the role of these
contacts in FA trafficking, and (iii) to evaluate the effect of Plin5 on lipid metabolism organelles. The central
hypothesis is that Plin5 utilizes a unique C-terminal domain to induce LD-Mito contacts that promote β-
oxidization during nutrient starvation by directing FA trafficking from LDs to Mito. The rationale for this project is
that identifying the mechanism and physiological role of LD-Mito contacts will result in strategies to treat lipid
storage/trafficking diseases. The central hypothesis will be tested by pursuing three specific aims. In Aim 1,
affinity purification mass spectrometry of Plin5 constructs lacking the minimal LD-Mito contact domain will be
performed to identify mitochondrial binding partners. Identified binding partners will then be assessed for a role
in LD-Mito contact formation. In Aim 2, fluorescent and radioactive pulse-chase assays will be utilized to
identify the physiological effect of Plin5 on FA storage, trafficking and metabolism. In Aim 3, multispectral
imaging will be utilized to evaluate the effect of Plin5 on the morphology and contacts between 5 organelles
involved in lipid metabolism. The expected outcomes are to define the mechanism by which Plin5 induces LD-
Mito contacts and to demonstrate the physiological function of these contacts. These results will have
important positive impact because they will establish a strong basis from which to further study dysregulated
lipid trafficking and suggest a framework from which to develop novel therapies for lipid-associated diseases.
To enable these research objectives, mentoring and technical/theoretical training will be provided by Dr.
Cohen, Dr. Coleman, and Dr. Klett whom are experts in multispectral imaging and lipid trafficking/metabolism
respectively. Career development will be facilitated by the Office of Postdoctoral Affairs through seminars and
workshops. The proposed research and training will be conducted at UNC Chapel Hill, which is well known for
its outstanding c...

## Key facts

- **NIH application ID:** 10251072
- **Project number:** 5F32GM136027-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Gregory Miner
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251072

## Citation

> US National Institutes of Health, RePORTER application 10251072, Mechanism of Lipid Droplet/ Mitochondria Contacts and Role of Perilipin 5 in Lipid Metabolism (5F32GM136027-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10251072. Licensed CC0.

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