# The Role of Lipid Transport in Autophagy Biogenesis Using Structural and Biochemical Approaches

> **NIH NIH F32** · YALE UNIVERSITY · 2021 · $20,386

## Abstract

Project Summary/Abstract
Macroautophagy is a vital process in which cells degrade malformed proteins and damaged macromolecules
and organelles using the lysosomal machinery. Autophagy initiates with formation of an autophagophore in the
vicinity of the endoplasmic reticulum (ER), followed by its expansion, maturation, and closure to form an
autophagosome. In the final step, the autophagosome fuses with a lysosome to initiate the degradation and
recycling of the engulfed cargoes. Although the later stages of autophagy have been studied thoroughly, little is
known about the early stages of phagophore biogenesis. Recently our group discovered that ATG2, a protein
essential for autophagy, contains an elongated cavity that can solubilize and transfer lipids between membranes
in vitro, and that it mediates lipid transfer from the ER to the nascent phagophore. Mutational impairment of
ATG2-mediated lipid transfer attenuates autophagy in vivo, suggesting this function is critical to autophagophore
growth. The long-term goal of this application is to elucidate the underlying molecular events that drive
phagophore membrane biogenesis by better understanding the role of lipid transport mediated by ATG2 and any
protein partners in autophagy. These protein partners include an integral membrane complex comprising
TMEM41B and VMP1, as well as other early autophagy proteins. In Aim 1, I will biochemically study the
mechanism of several key early-autophagy proteins at sites of autophagophore initiation to better understand
the machinery required to support membrane expansion. In Aim 2, I will use structural and biochemical
approaches to inspect the specific function of an ER-localized integral membrane complex, TMEM41B and
VMP1 proteins, which has been shown to be essential in autophagophore biogenesis.

## Key facts

- **NIH application ID:** 10169237
- **Project number:** 5F32GM137568-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Alireza Ghanbarpour
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $20,386
- **Award type:** 5
- **Project period:** 2020-06-01 → 2021-09-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169237

## Citation

> US National Institutes of Health, RePORTER application 10169237, The Role of Lipid Transport in Autophagy Biogenesis Using Structural and Biochemical Approaches (5F32GM137568-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10169237. Licensed CC0.

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