# Clu forms a dynamic new ribonucleoprotein particle directly involved in mitochondrial function

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2022 · $324,105

## Abstract

PROJECT SUMMARY: Fully functional mitochondria are critically important for cells, and particularly
important for tissues with high-energy demands such as muscle, neurons, and the developing embryo. As
such, mitochondrial dysfunction is often associated with disease, such as neurodegeneration, cardiovascular
disease and diabetes. Mitochondria work in concert with the nucleus and must import hundreds of nucleus-
encoded products to supplement their own small genome. We have developed Drosophila as a model system to
study mitochondria and our long-term goal is to understand the molecular mechanisms that control
mitochondrial function during tissue homeostasis and development. We have found the Drosophila protein
Clueless (Clu) is required to support mitochondrial function. Clu is highly conserved from yeast to human and
Clu family members are ribonucleoproteins that preferentially bind nucleus-encoded mRNAs destined for
mitochondria. Clu forms dynamic, large, mitochondria-associated particles in the cytoplasm. Our broad
objectives for this proposal are to determine how particles form and what role they play in supporting
mitochondrial function and protein import. Drosophila clu mutants are sick and sterile with damaged
mitochondria. Clu associates with proteins located in the mitochondrial outer membrane, including the
translocase responsible for protein import. Clu also associates with the ribosome at the outer membrane. We
hypothesize that Clu particle formation is important for regulating mRNA localization and protein import.
To test this hypothesis, our first Aim defines Clu particle dynamics and the signals that regulates it using
microscopy, genetics and molecular biology. Our second Aim examines how Clu particles contribute to mRNA
regulation using microscopy, molecular biology and biochemistry. Our third Aim uses molecular biology,
biochemistry and genetics to examine how Clu particles regulate mitochondrial protein levels. The knowledge
we expect to gain from this proposal on Clu particle regulation will be a transformative step forward because so
little is known about the ribonucleoproteins involved in mitochondrial protein import, and Clu particles
represent an undefined, novel cytoplasmic particle critical for mitochondrial function. Knowledge gained from
the research proposed here will significantly advance our understanding of how mitochondria-localized
mRNAs are regulated, translated and imported, which is a basic, fundamental process important for
mitochondrial function in all cells.

## Key facts

- **NIH application ID:** 10434693
- **Project number:** 5R01GM127938-04
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Rachel Tafel Cox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $324,105
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434693

## Citation

> US National Institutes of Health, RePORTER application 10434693, Clu forms a dynamic new ribonucleoprotein particle directly involved in mitochondrial function (5R01GM127938-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10434693. Licensed CC0.

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