# A mitochondrial membrane-spanning ternary complex regulates mitochondrial motility

> **NIH NIH R21** · STANFORD UNIVERSITY · 2020 · $234,750

## Abstract

We seek to understand the regulatory mechanisms that control the movements of mitochondria
in cells. Mitochondria move and undergo fission and fusion in all eukaryotic cells, but the need to
supply mitochondria to the far-flung extremities of neurons creates a particular urgency for
mitochondrial transport in neurons. Defects in mitochondrial movements can give rise to
peripheral neuropathies and degeneration 1. We and our colleagues have identified a protein
complex that includes milton, Miro, and the kinesin-1 heavy chain (KHC) and have shown that
this complex is essential for the anterograde ((+)-end directed) transport of mitochondria in
neurons. We have determined that Miro is degraded by the proteasome via PINK1/Parkin-
dependent phosphorylation and ubiquitination. Additionally, and most relevantly to this proposal,
we have obtained exciting preliminary results demonstrating a novel machinery spanning both
the mitochondrial outer and inner membranes that stabilizes Miro. We now propose to
further our understanding of this machinery by examining in greater detail how it is regulated by
intracellular signals and neuronal activity. These signaling pathways are crucial to the ability of
mitochondria to properly distribute themselves within a cell and to permit cells to respond to
stresses and changes in activity. Aim 1: To determine the nature of the ternary complex
spanning the mitochondrial membranes. Aim 2: To determine the regulatory signals of
this ternary complex. Aim 3: To determine the functional relevance of this ternary complex.

## Key facts

- **NIH application ID:** 9861204
- **Project number:** 5R21AG061315-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** XINNAN WANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,750
- **Award type:** 5
- **Project period:** 2019-02-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861204

## Citation

> US National Institutes of Health, RePORTER application 9861204, A mitochondrial membrane-spanning ternary complex regulates mitochondrial motility (5R21AG061315-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9861204. Licensed CC0.

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