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SHR Neuro Cancer Cardio Lipid Metab Microb

Kiessling, M; Gindlhuber, J; Sintou, A; Matzer, I; Radulović, S; Trummer-Herbst, V; Ajdari, A; Voglhuber-Höller, J; Holzer, M; Rodriguez, TA; Leitinger, G; Zirlik, A; Bers, DM; Sattler, S; Ljubojevic-Holzer, S.
A transmission electron microscopy platform for assessing mitochondrial and nuclear architecture in cardiomyocytes.
Cell Rep Methods. 2025; 101212 Doi: 10.1016/j.crmeth.2025.101212
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Leading authors Med Uni Graz
Holzer Senka
Kießling Mara Luisa
Sattler Susanne
Co-authors Med Uni Graz
Ajdari Andonita
Gindlhuber Jürgen
Holzer Michael
Leitinger Gerd
Matzer Ingrid
Radulovic Snjezana
Trummer-Herbst Viktoria
Voglhuber Julia
Zirlik Andreas
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Abstract:
Mitochondria are central to cardiomyocyte function, and their spatial organization regulates nuclear signaling and gene transcription, holding potential for novel cardioprotective interventions. We developed a transmission electron microscopy platform optimized for resolving mitochondrial subpopulations and nuclear architecture in adult cardiomyocytes. This approach reliably captures longitudinal sections containing the center of the nucleus and perinuclear regions, enabling consistent imaging of subcellular nanostructures, assessment of pharmacological effects within the same organism, and visualization of extracellular vesicles carrying dysfunctional mitochondria. Integrated with an analysis workflow employing machine learning-based segmentation for annotation, the method allows automated quantification of mitochondrial and nuclear architecture and positioning. Using Drp1-deficient mice with impaired mitochondrial fission, we demonstrate this tool's ability to uncover nanoscale remodeling of mitochondria and nuclei under stress. Our platform overcomes challenges in electron microscopy analysis, providing a powerful resource to interrogate mitochondrial-nuclear dynamics in cardiac (patho)physiology. These insights will inform therapeutic targeting of bioenergetic failure.

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