# Mitochondrial fusion protein MFN2 prevents platelet death and dysfunction

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $381,250

## Abstract

Abstract
 Mitochondrial dysfunction is associated with numerous diseases, including disorders of thrombosis and
hemostasis. Platelets inherit fully functional mitochondria from megakaryocytes, yet how megakaryocytes
maintain mitochondrial integrity and function during their unique developmental process is unknown. Genetic
studies have associated the mitochondrial maintenance and fusion protein Mitofusin 2 (MFN2) with platelet
counts and cardiovascular disease. Our preliminary data show that loss of MFN2 in human platelets is
associated with accelerated platelet death in vitro. Knockout of MNF2 in mice reduced platelet survival, and
impaired hemostasis and thrombosis. Preliminary data suggest a mitochondrial role: loss of MFN2 disrupted
mitochondrial morphology in megakaryocytes, and impaired mitochondrial function in platelets.
 In Aim 1 we test the hypothesis that MFN2 maintains mitochondrial integrity and function during
megakaryocyte development to ensure platelets inherit fully functional and long-lived mitochondria. In Aim 2
we test the hypothesis that loss of MFN2 leads to platelet death, dysfunction, and altered hemostasis and
thrombosis. Because MFN2 is especially important in adapting to metabolic stress, we will test each of these
hypotheses under normal conditions and during metabolic stress. Each aim will have a mouse and human
component: for mouse studies we will use platelet/megakaryocyte specific MFN2 knockouts, and for human
studies we will utilize primary cells harboring a genetic variant that significantly reduces MFN2 expression in
platelets.
 This work is significant because the results may lead to new approaches to target disorders of thrombosis
and hemostasis, and improve platelet production and storage. This work is innovative: we will examine
mitochondrial fusion, a novel pathway regulating platelet survival and function in health, during metabolic
stress, and in transfused platelets. We will use innovative methods to examine mitochondrial function in new
and circulatory aged platelets. Our studies will provide new insights into how MFN2 affects platelet death and
dysfunction, an important step into understanding why human MFN2 variants are associated with platelet
counts and cardiovascular disease.

## Key facts

- **NIH application ID:** 9859455
- **Project number:** 5R01HL144957-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** JESSE ROWLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859455

## Citation

> US National Institutes of Health, RePORTER application 9859455, Mitochondrial fusion protein MFN2 prevents platelet death and dysfunction (5R01HL144957-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9859455. Licensed CC0.

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