# MTFR2 in the control of mitochondrial dynamics and mitotic spindle integrity

> **NIH NIH R15** · UNIVERSITY OF TOLEDO · 2024 · $42,419

## Abstract

PROJECT SUMMARY
The PI’s lab has long-term interest in how aberrant mitosis occurs and its relationship to cancer cell heterogeneity.
Our prior work has contributed to current understanding about the spindle assembly checkpoint, a critical
mechanism to prevent chromosomal instability. Many other factors also help control the fidelity of chromosome
segregation. Most relevant to this proposal, there was some evidence indicating that defects in mitochondrial
dynamics affect chromosome segregation, but detailed mechanistic analysis is still lacking. Mitochondrial Fission
Regulator 2 (MTFR2, also named FAM54A or DUFD1) was retrieved as a gene co-transcribed with key
centromere/kinetochore components in our previous study. Such association suggested a role of MTFR2 in
mitosis. However, despite the name, not much is known about the biological function or regulation of MTFR2 at
the cellular level. Our preliminary results demonstrated that MTFR2 regulates mitochondrial fission in a Drp1-
dependent manner. We also found that many cancer-occurring MTFR2 variants are defective in triggering
mitochondrial fission. In addition, conditional MTFR2 knockout by inducible Cas9/CRISPR resulted in loss of
astral microtubules and multipolar spindles during mitosis, resulting in chromosome missegregation. Building
upon the preliminary data, we hypothesize that MTFR2 plays critical roles in coordinating mitochondrial
fission and chromosome segregation during mitosis. The overall objective of this project is to further clarify
the MTFR2 activity in mitochondrial fission and mitotic progression, and conversely how cell cycle machinery
regulates MTFR2 activity. Aim 1 experiments will elucidate the activities and mechanisms of MTFR2 in
mitochondrial fission especially during mitosis, and Aim 2 experiments will investigate how compromising MTFR2
activity in mitosis affects chromosome missegregation and taxol resistance. The proposal is expected to expand
our understanding about mitochondrial fission mechanisms, and provide insights how mitochondria and
chromosome inheritance are coordinated during mitosis to ensure healthy daughter cells. The collaborative
project will provide an invaluable platform at the University of Toledo to support and train undergraduate students
for hands-on research experience.

## Key facts

- **NIH application ID:** 11031534
- **Project number:** 3R15GM147878-01S2
- **Recipient organization:** UNIVERSITY OF TOLEDO
- **Principal Investigator:** Song-Tao Liu
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,419
- **Award type:** 3
- **Project period:** 2022-12-10 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11031534

## Citation

> US National Institutes of Health, RePORTER application 11031534, MTFR2 in the control of mitochondrial dynamics and mitotic spindle integrity (3R15GM147878-01S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11031534. Licensed CC0.

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