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Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
Desmoglein-2 deficiency drives mitochondrial morphological remodeling in cardiomyocytes
Alexandre Gonçalves1, Elaine Zhelan Chen2, Hosna Rastegarpouyani3
1RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
Summary
Pathogenic variants in desmoglein-2 (DSG2) cause arrhythmogenic cardiomyopathy (ACM). This study reveals DSG2 deficiency impairs mitochondrial function, particularly in the right ventricle, highlighting a desmosomal-mitochondrial axis in ACM.
Area of Science:
- Cardiology
- Mitochondrial Biology
- Genetics
Background:
- Pathogenic variants in desmoglein-2 (DSG2) are a primary cause of arrhythmogenic cardiomyopathy (ACM).
- Mitochondrial dysfunction is increasingly implicated in DSG2-associated ACM, but chamber-specific remodeling is not well understood.
Purpose of the Study:
- To investigate chamber-specific mitochondrial remodeling in DSG2-linked arrhythmogenic cardiomyopathy using a mouse model.
- To define the impact of DSG2 deficiency on mitochondrial structure and function within the ventricles.
Main Methods:
- Utilized a homozygous Dsg2 mutant (Dsg2mut/mut) mouse model.
- Performed re-analysis of cardiomyocyte snRNAseq data to assess mitochondrial gene expression.
- Conducted transmission electron microscopy for ultrastructural analysis of mitochondria.
Main Results:
- Downregulation of mitochondrial transcripts related to fusion/fission, calcium handling, mitophagy, and electron transport chain (ETC) assembly was observed.
- Dsg2mut/mut hearts showed increased numbers of smaller, irregularly shaped, and disorganized mitochondria compared to wildtype.
- Mitochondrial alterations were chamber-dependent, with the right ventricle (RV) exhibiting more pronounced changes than the left ventricle (LV).
Conclusions:
- Mitochondrial remodeling is a key feature of DSG2 deficiency and arrhythmogenic cardiomyopathy.
- A desmosomal-mitochondrial axis is implicated in ACM pathogenesis.
- Mitochondrial pathways represent potential therapeutic targets for DSG2-associated ACM.
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