# Discovery of a novel role of VPS13D in Autophagy

> **NIH NIH F30** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $31,731

## Abstract

Abstract/Project Summary
Defects in autophagy, the self-degradation of cellular components, are linked to multiple disorders such as
cancer, diabetes and neurodegenerative diseases. Autophagosomes, containing cargo marked for
degradation, fuse with lysosomes to recycle cell resources, such as protein aggregates and damaged
organelles. However, we know little about the mechanisms that regulate the association between autophagic
cargoes and autophagosome formation. Here, I investigate the role of vps13d, an essential gene with relatively
unknown function, in context-specific autophagy and cell death in the developing Drosophila intestine. Proteins
that regulate autophagy and cell death are of particular interest given the roles they play in tumorigenesis.
Previous studies of VPS13D identified a role in the clearance of mitochondria by autophagy, also known as
mitophagy. Intriguingly, VPS13D also appears to be involved in dissolution of membrane contacts that are
associated with autophagosome formation. Furthermore, little is known about the role of VPS13D in
associating autophagy-bound cargo with the site of autophagosome formation, despite having links to the core
autophagy machinery. I hypothesize that VPS13D facilitates context-dependent autophagy by associating
ubiquitinated cargo with the autophagic machinery and disassembling membrane contact sites at the
phagosome assembly site (PAS). Here I propose to determine if VPS13D functions as an autophagy receptor
for ubiquitinated cargo and determine the relationship between VPS13D and membrane contact modulator
Vacuole Membrane Protein 1 (VMP1). The association of VPS13D and mutations in other factors that regulate
autophagic cargo recruitment with human disorders illustrates the importance of studying VPS13D function.

## Key facts

- **NIH application ID:** 10353370
- **Project number:** 5F30CA239374-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** James L Shen
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,731
- **Award type:** 5
- **Project period:** 2019-03-05 → 2025-03-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353370

## Citation

> US National Institutes of Health, RePORTER application 10353370, Discovery of a novel role of VPS13D in Autophagy (5F30CA239374-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10353370. Licensed CC0.

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