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Updated: Mar 29, 2026
Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs
Published on: August 15, 2025
NFAT4-dependent miR-324-5p regulates mitochondrial morphology and cardiomyocyte cell death by targeting Mtfr1
1Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, China.
Abstract:
Emerging evidence suggest that the abnormal mitochondrial fission participates in pathogenesis of cardiac diseases, including myocardial infarction and heart failure. However, the molecular components regulating mitochondrial network in heart remain largely unidentified. Here we report that NFAT4, miR-324-5p and mitochondrial fission regulator 1 (Mtfr1) function in one signaling axis that regulates mitochondrial morphology and cardiomyocyte cell death. Knocking down Mtfr1 suppresses mitochondrial fission, apoptosis and myocardial infarction. Mtfr1 is a direct target of miR-324-5p, and miR-324-5p attenuates mitochondrial fission, cardiomyocyte apoptosis and myocardial infarction by suppressing Mtfr1 translation. Finally, we show that transcription factor NFAT4 inhibits miR-324-5p expression. Knockdown of NFAT4 suppresses mitochondrial fission and protects cardiomyocyte from apoptosis and myocardial infarction. Our study defines the NFAT4/ miR-324-5p/Mtfr1 axis, which participates in the regulation of mitochondrial fission and cardiomyocyte apoptosis, and suggests potential new treatment avenues for cardiac diseases.
Insights
Abnormal mitochondrial fission contributes to heart disease. This study identifies the NFAT4/miR-324-5p/Mtfr1 axis regulating mitochondrial fission and cardiomyocyte death, offering potential therapeutic targets for cardiac conditions.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Dynamics
- Molecular Cardiology
Background:
- Abnormal mitochondrial fission is implicated in cardiac diseases like myocardial infarction and heart failure.
- The specific molecular regulators of mitochondrial networks in the heart are not fully understood.
Purpose of the Study:
- To identify key molecular components regulating mitochondrial morphology and cardiomyocyte apoptosis in the heart.
- To elucidate the signaling axis involving NFAT4, miR-324-5p, and Mtfr1 in cardiac pathogenesis.
Main Methods:
- Investigated the role of NFAT4, miR-324-5p, and mitochondrial fission regulator 1 (Mtfr1) in regulating mitochondrial morphology.
- Utilized knockdown experiments to assess the impact of Mtfr1 and NFAT4 on mitochondrial fission, apoptosis, and myocardial infarction.
- Determined the regulatory relationship between miR-324-5p and Mtfr1, and between NFAT4 and miR-324-5p.
Main Results:
- Knocking down Mtfr1 reduced mitochondrial fission, apoptosis, and myocardial infarction.
- miR-324-5p directly targets Mtfr1, attenuating mitochondrial fission and cardiomyocyte apoptosis.
- NFAT4 was found to inhibit miR-324-5p expression, and its knockdown protected against mitochondrial fission and cardiomyocyte death.
Conclusions:
- The NFAT4/miR-324-5p/Mtfr1 signaling axis is a critical regulator of mitochondrial fission and cardiomyocyte apoptosis.
- This axis represents a potential therapeutic target for treating cardiac diseases such as myocardial infarction and heart failure.
