# Milton/Trak 1/2 Protein and the Transport of Mitochondria

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $371,700

## Abstract

Work from this lab and others has established that mitochondrial motility is governed by a motor/adaptor
complex that couples both kinesin and dynein motors to the mitochondrial surface. Much, however, remains
unknown about how regulation of that complex determines when and where a mitochondrion will stop, or why
some mitochondria are long-term stationary, while others only pause briefly before continuing to move.
Anchoring proteins are known that can hold mitochondria in place, but the interplay of anchoring proteins and
mitochondrial motors is poorly understood. This proposal seeks to understand mechanisms that regulate the
assembly of the motor/adaptor complex and signaling pathways that can turn off those motors. The proposal
also seeks to understand when mitochondria are merely passively stationary and when they are being actively
held in place by an anchor. The exceptional shapes of neurons makes mitochondrial motility and its regulation
particularly important so that the branches of axons and dendrites can be properly supplied with mitochondria
and certain locations with high energetic demand, such as synapses, can have increased density of
mitochondria. This proposal therefore places special emphasis on how mitochondrial dynamics are regulated
in axons and on signals that may localize mitochondria to synapses. To better understand mitochondrial
regulation, the proposal introduces two novel approaches. One approach is the misdirection of the
mitochondrial motor/adaptor complex to peroxisomes so that assembly and regulation of the complex can be
studied and mutated away from the endogenous mitochondrial proteins. The other new approach is to use a
heterodimerizing agent to attach a constitutively active kinesin motor to mitochondria and thereby test whether
mitochondria are being actively held in place by an anchor. In addition, this proposal introduces two new
factors that govern the motility of mitochondria, a protein that anchors mitochondria to the actin cytoskeleton,
and a kinase that regulates the localization of mitochondria at synapses. In Aim 1 we propose to study how a
GTPase domain of Miro regulates the ability of the complex to assemble and what physiological significance
there is to the GTPase activity. In Aim 2 we investigate competing models for how elevated Ca2+and the
PINK1/Parkin pathway cause mitochondria to stop and ask whether or not they immobilize mitochondria with
anchoring proteins. In Aim 3 we investigate the mechanism by which Aurora kinase B inhibits mitochondrial
movement and thereby promotes the localization of mitochondria to synapses.

## Key facts

- **NIH application ID:** 10080033
- **Project number:** 5R01GM069808-15
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Thomas L. Schwarz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $371,700
- **Award type:** 5
- **Project period:** 2004-09-20 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080033

## Citation

> US National Institutes of Health, RePORTER application 10080033, Milton/Trak 1/2 Protein and the Transport of Mitochondria (5R01GM069808-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10080033. Licensed CC0.

---

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