Related Experiment Video
Updated: Aug 6, 2026
07:14
A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
MLL4 protects cardiomyocytes against ischemia-reperfusion injury through STAT3-mediated mitochondrial function
Qiu-Yu Pang1, Xiang-Min Meng1, De-Yong Li1
1Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
Redox Biology
|July 25, 2026
Summary
Mixed-lineage leukemia 4 (MLL4) protects against myocardial ischemia-reperfusion injury (MIRI). MLL4 deficiency worsens MIRI by impairing STAT3-mediated mitochondrial function, highlighting MLL4 as a therapeutic target.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Molecular Medicine
Background:
- Myocardial ischemia-reperfusion injury (MIRI) is a significant clinical challenge with limited targeted therapies.
- Mixed-lineage leukemia 4 (MLL4) is a histone methyltransferase involved in gene regulation.
Purpose of the Study:
- To investigate the role of MLL4 in the pathogenesis of MIRI.
- To elucidate the molecular mechanisms by which MLL4 influences MIRI.
Main Methods:
- Utilized cardiomyocyte-specific Mll4 knockout mice and an in vivo ischemia-reperfusion (I/R) model.
- Performed in vitro experiments using neonatal rat cardiomyocytes (NRCMs) under hypoxia/reoxygenation (H/R).
- Integrated Cleavage Under Targets and Tagmentation sequencing (CUT&Tag-seq) and RNA sequencing (RNA-seq) analyses.
Main Results:
- MLL4 expression was upregulated following I/R in cardiac tissue.
- Mll4 deficiency exacerbated both acute and chronic MIRI, increasing mitochondrial dysfunction and apoptosis.
- MLL4 deficiency reduced H3K4me1 and H3K27ac at the Stat3 locus, impairing STAT3 transcription and mitochondrial homeostasis.
Conclusions:
- MLL4 plays a critical protective role in MIRI by epigenetically regulating STAT3.
- Targeting MLL4 may represent a novel therapeutic strategy for mitigating reperfusion injury.