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Assessing the effects of mitofusin 2 deficiency in the adult heart using 3D electron tomography
Siavash Beikoghli Kalkhoran1,2,3, Andrew R Hall1,2,3, Ian J White4
1The Hatter Cardiovascular Institute University College London, London, United Kingdom.
Abstract:
The effects of mitofusin 2 (MFN2) deficiency, on mitochondrial morphology and the mitochondria-junctional sarcoplasmic reticulum (jSR) complex in the adult heart, have been previously investigated using 2D electron microscopy, an approach which is unable to provide a 3D spatial assessment of these imaging parameters. Here, we use 3D electron tomography to show that MFN2-deficient mitochondria are larger in volume, more elongated, and less rounded; have fewer mitochondria-jSR contacts, and an increase in the distance between mitochondria and jSR, when compared to WT mitochondria. In comparison to 2D electron microscopy, 3D electron tomography can provide further insights into mitochondrial morphology and the mitochondria-jSR complex in the adult heart.
Insights
Mitofusin 2 (MFN2) deficiency alters heart mitochondria shape and reduces connections with the sarcoplasmic reticulum. 3D electron tomography reveals these changes more effectively than 2D methods.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Dynamics
- Cellular Ultrastructure
Background:
- Mitofusin 2 (MFN2) plays a critical role in mitochondrial fusion and maintaining the mitochondria-junctional sarcoplasmic reticulum (jSR) complex.
- Previous studies using 2D electron microscopy provided limited insights into MFN2's effects on mitochondrial morphology and jSR interactions.
- A 3D spatial assessment is crucial for understanding these complex cellular structures.
Purpose of the Study:
- To investigate the impact of MFN2 deficiency on mitochondrial morphology in the adult heart using 3D electron tomography.
- To assess the alterations in the mitochondria-junctional sarcoplasmic reticulum (jSR) complex in MFN2-deficient hearts.
- To compare the efficacy of 3D electron tomography versus 2D electron microscopy for studying these parameters.
Main Methods:
- Utilized 3D electron tomography for high-resolution imaging of cardiac mitochondria.
- Compared MFN2-deficient (MFN2-/-) adult heart mitochondria with wild-type (WT) mitochondria.
- Quantified mitochondrial volume, shape, and the number and proximity of mitochondria-jSR contacts.
Main Results:
- MFN2-deficient mitochondria exhibited increased volume, elongation, and reduced roundness compared to WT.
- A significant decrease in mitochondria-jSR contacts was observed in MFN2-deficient hearts.
- The distance between mitochondria and jSR increased in the absence of MFN2.
Conclusions:
- 3D electron tomography provides superior insights into mitochondrial morphology and mitochondria-jSR complex alterations compared to 2D methods.
- MFN2 deficiency profoundly impacts cardiac mitochondrial structure and its interaction with the jSR.
- These findings highlight the importance of MFN2 in maintaining cardiac mitochondrial integrity and function.
