# Studying the mitochondrial motor/adaptor complex by misdirecting it to peroxisomes

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2020 · $8,302

## Abstract

Abstract
This proposal examines mechanisms that regulate how mitochondria move within cells. Mitochondria are
actively transported in all cells including neurons. Disrupted mitochondrial trafficking has been linked to axonal
degeneration, dysfunctional synapses, and the pathologies of neurodegenerative disorders, including
Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. These studies illustrate the
critical nature of maintaining the proper regulation of mitochondrial trafficking for neuronal health. Miro, also
called RhoT1/2, is an essential protein for mitochondrial motility. Miro is a mitochondrial outer membrane
protein with two GTPase domains that are often presumed to be regulatory switches but whose functions have
remained obscure despite over a decade of study. Analysis of this protein has been confounded by several
factors: 1) interpretation of overexpression studies is complicated by the presence of endogenous Miro; 2)
there are two potentially redundant isoforms of Miro in mammalian cells; and 3) removal of both isoforms of
Miro is lethal. To gain a better understanding of the regulation of mitochondrial trafficking, I have misdirected
Miro to peroxisomes and found that it can confer on the normally stationary peroxisomes the ability to be
transported by the motor complex normally found on mitochondria. By mutating the first GTPase domain of
Miro, I have discovered that it regulates the ability of the Kinesin-1 motor to associate with the Miro complex. I
now propose the following aims: 1) To investigate further the effects of Miro and its GTPase domains, including
examining the mechanism by which it regulates kinesin binding; 2) To test competing hypotheses for how
cytosolic Ca2+ regulates mitochondrial motility, and 3) To determine whether the Miro-containing motor/adaptor
complex is responsible for the enrichment of mitochondria at synapses. This proposal thereby seeks to provide
insights into the fundamental processes by which a neuron distributes mitochondria to support the energetic
needs of all its parts.
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## Key facts

- **NIH application ID:** 10222445
- **Project number:** 3F31GM126681-02S1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Kayla Davis
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $8,302
- **Award type:** 3
- **Project period:** 2018-08-01 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222445

## Citation

> US National Institutes of Health, RePORTER application 10222445, Studying the mitochondrial motor/adaptor complex by misdirecting it to peroxisomes (3F31GM126681-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10222445. Licensed CC0.

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