# Studying Mitochondrial Dynamics and Energetics During Cardiac Reprogramming

> **NIH NIH F32** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $78,892

## Abstract

Studying Mitochondrial Dynamics and Energetics During Cardiac Reprogramming
Abstract: Direct reprogramming of cardiac fibroblasts (CFs) to induced cardiomyocytes (iCMs) shows promise
for the treatment of cardiac injury, such as a myocardial infarction (MI). Barriers to clinical application include low
reprogramming efficiency and relative immaturity of iCMs. A metabolic shift from glycolysis to mitochondrial
respiration is required to transdifferentiate CFs to mature iCMs, but this aspect of cardiac reprogramming remains
understudied. In preliminary experiments, mitochondria in native CMs showed higher fusion activity, more
organizational complexity and higher trans-membrane potential than native CFs. By day 15 of standard cardiac
reprogramming, only some of these changes are observable in reprogrammed cells. Knockdown of the
mitochondrial fission regulator Mtfr1l led to improved reprogramming efficiency and iCM maturation. I therefore
propose to characterize a time course of mitochondrial structural and functional changes during cardiac
reprogramming. Additionally, I will investigate the molecular mechanisms of Mtfr1l as a barrier to cardiac
reprogramming and evaluate other mitochondrial perturbations for impact on reprogramming efficiency and iCM
maturation. This work will offer insights into the mitochondrial regulation of cardiac reprogramming and how
mitochondria can be harnessed to improve reprogramming strategies. These insights will bring us closer to
clinical translation of these strategies to benefit patients after MI.

## Key facts

- **NIH application ID:** 10996486
- **Project number:** 1F32HL176045-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Brian M Spurlock
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $78,892
- **Award type:** 1
- **Project period:** 2024-09-15 → 2027-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996486

## Citation

> US National Institutes of Health, RePORTER application 10996486, Studying Mitochondrial Dynamics and Energetics During Cardiac Reprogramming (1F32HL176045-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10996486. Licensed CC0.

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