# Mitochondrial Quality Control by Drp1

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $319,313

## Abstract

Abstract
Mitochondria actively generate ATP via oxidative phosphorylation and constantly undergo high levels of
oxidative stress. Lysosomal degradation of mitochondria is a key quality control that inhibits the accumulation
of mitochondrial damage. Understanding mitochondrial quality control is critical and urgent because its defects
have been linked to many neurological disorders such as Alzheimer's disease, Parkinson's disease and
amyotrophic lateral sclerosis. Our preliminary data led us to hypothesize that a brain-specific, lysosome-
associated isoform of Drp1 GTPase, termed lysoDrp1, enhances transport of mitochondria to lysosomes by
increasing the proximity between these two organelles. In this proposed investigation, we will test this
hypothesis in two specific aims. In the first aim, we will determine how lysoDrp1 delivers mitochondria into
lysosomes (1.1), how GTP regulates lysoDrp1 (1.2), and what recruits lysoDrp1 to lysosomes (1.3). In the
second aim, we will determine the function of lysoDrp1 in mitochondrial turnover in neurons (2.1), the role of
lysoDrp1-meidated quality control for energy metabolism in neurons (2.2), and the impact of lysoDrp1 on the
survival of neurons (2.3). To successfully accomplish these aims, we will use innovative approaches including
lysoDrp1-specific mouse knockout generated by CRISPR/Cas9, a fluorescent biosensor for the transport of
mitochondria to lysosomes and Drp1-knockout cells reconstituted with single, specific Drp1 isoforms. This work
will have a significant impact on translating the mechanistic information of mitochondrial quality control into
therapeutic interventions for human diseases.

## Key facts

- **NIH application ID:** 10115066
- **Project number:** 5R01GM123266-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Hiromi Sesaki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $319,313
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115066

## Citation

> US National Institutes of Health, RePORTER application 10115066, Mitochondrial Quality Control by Drp1 (5R01GM123266-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10115066. Licensed CC0.

---

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