# The Roles of the Dynamin-Related Protein Vps1 and the ESCRT Complex in Microautophagy

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $293,688

## Abstract

Microautophagy is a poorly-characterized autophagic pathway defined by direct invagination of
vacuolar (fungi) or lysosomal (higher eukaryotes) membrane for engulfment and degradation of
organelles and cytosolic components. Microautophagy is required for cell survival under
conditions of stress, such as nutrient limitation, and for resumption of cell growth on recovery
from stress. Strikingly, microautophagy is also a key regulator of TOR signaling, which plays
well-established roles in growth, survival and lifespan control. The molecular mechanism of
microautophagy and how it regulates TOR signaling is not understood. Our long-term goal is to
understand the mechanism of microautophagy and how microautophagy is harnessed to
regulate signaling cascades required for growth and development. Our preliminary data
demonstrates that the membrane remodeling required for microautophagy depends on the
dynamin-related protein (DRP) Vps1 and the ESCRTIII component Snf7. DRPs and ESCRTs
are fascinating membrane remodeling machines that are vital for several fundamental cellular
processes including membrane trafficking, mitochondrial dynamics, cytokinesis and viral
budding. DRPs and ESCRTs both couple membrane deformation to self-assembly. Deficiencies
in DRPs and ESCRTs are associated with numerous pathologies due to their central roles in
homeostasis, including neurodegenerative disorders. Our central hypothesis is that the
functional interaction between DRPs and ESCRTs forms the molecular basis for membrane
invagination in microautophagy. Furthermore, we propose that nutrient and stress signaling
pathways converge on Vps1 and ESCRT to regulate their novel function in microautophagy to,
ultimately, control TOR signaling and cell growth. Using genetic, proteomic, cytological and
structural approaches, we will characterize the mechanism of recruitment of DRP and ESCRT to
sites of microautophagy, as well as the regulatory determinants of their function in TOR
signaling. Completion of this work will provide an in-depth understanding of the machinery
required for microautophagy. It will shed mechanistic light on novel aspects of DRP and ESCRT
function that may have broad implications for membrane remodeling processes in general.
Finally, this work will provide important insight into the mechanisms whereby microautophagy
regulates TOR signaling. Dysregulation of TOR signaling is associated with several human
cancers. Hence, the machinery of microautophagy, as a regulator of TOR signaling, represents
a novel target for development of anticancer and antifungal drugs.

## Key facts

- **NIH application ID:** 9942474
- **Project number:** 5R01GM120102-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Marijn Gerard Johannes Ford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,688
- **Award type:** 5
- **Project period:** 2016-09-20 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942474

## Citation

> US National Institutes of Health, RePORTER application 9942474, The Roles of the Dynamin-Related Protein Vps1 and the ESCRT Complex in Microautophagy (5R01GM120102-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9942474. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*