# Molecular Mechanisms of FUNDC1-Mediated Mitophagy

> **NIH NIH F31** · DARTMOUTH COLLEGE · 2022 · $46,752

## Abstract

ABSTRACT
 Autophagy is a lysosome-mediated pathway that selectively targets and degrades cytoplasmic content.
Identification of autophagy targets is a critical facet of cellular homeostasis and is mediated by selective
autophagy receptors. Immense progress has been made in characterizing soluble autophagy receptors.
However, mechanisms of recently discovered membrane-embedded receptor Fun14 domain-containing 1
(FUNDC1) remains widely unknown. Located on the outer mitochondrial membrane, FUNDC1 mediates
autophagic turnover of mitochondria, termed mitophagy. FUNDC1-mediated mitophagy is induced in diverse
pathologies and developmental programs. For example, previous studies have demonstrated a physiological
role for FUNDC1-mediated mitophagy in hypoxia-related pathologies, including cancer and ischemia-reperfusion
injury. Preliminary results suggest that FUNDC1-mediated mitophagy is molecularly distinct from other forms of
mitophagy. The overall objective of this proposal is to elucidate the molecular mechanisms of hypoxia-induced
selective autophagy pathways through the characterization of FUNDC1 function. In Aim 1, a domain analysis
approach will be performed to identify functionally important regions of FUNDC1 required for hypoxia-induced
mitophagy. These studies will dissect potential activation events that enable activation of FUNDC1. In Aim 2,
CRISPR-Cas9 technology for high-throughput genetic screens will be used to identify modulators of FUNDC1
turnover. Novel genetic factors that modulate FUNDC1-mediated mitophagy will be characterized for their
function. Taken together, the proposed experiments will provide insight to elucidate mechanisms of hypoxia-
induced selective autophagy and expand putative therapeutic targets for autophagy in hypoxic-related human
pathologies. With the proposed training plan, I will enhance the skills needed to progress my scientific research
career including laboratory technical skills, experimental design, science communication, and mentorship.
Dartmouth College and my mentorship team are well-equipped to ensure success of my research project and
progression to the next step of my academic career as a postdoctoral researcher.

## Key facts

- **NIH application ID:** 10461452
- **Project number:** 1F31GM143849-01A1
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Jose M Delgado
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10461452

## Citation

> US National Institutes of Health, RePORTER application 10461452, Molecular Mechanisms of FUNDC1-Mediated Mitophagy (1F31GM143849-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10461452. Licensed CC0.

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