Bioenergetic and Metabolic Impairments in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Duchenne Muscular Dystrophy Patients
Abstract
:1. Introduction
2. Results
2.1. Metabolic Profiling Revealed a Bioenergetic Impairment of DMD iPSC-CMs
2.2. The Metabolic/Energy Status of the iPSC-CMs Correlates with Their Electrophysiological Characteristics
2.3. Stable-Isotope Glucose Tracing Reveals Decreased Oxidative Status in DMD Cardiomyocytes
2.4. DMD-Derived iPSC-CMs Demonstrate Oxidative Phosphorylation Deficiency
2.5. Mitochondria Structural and Functional Alterations in Energy-Depleted DMD iPSC-CMs
3. Discussion
3.1. Decreased PCr in DMD CMs
3.2. Mitochondrial Dysfunction in DMD CMs
3.3. Changes in Mitochondrial Content and Morphology in DMD CMs
3.4. The Link between Dystrophin Mutation and Mitochondrial Structural and Functional Aberrations
3.5. The Arrhythmias in DMD Cardiomyocytes
3.6. Do Fibroblasts “Remember” the Age of the DMD Patient?
4. Materials and Methods
4.1. The Experimental Groups
4.2. Experimental Protocols
4.3. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Willi, L.; Abramovich, I.; Fernandez-Garcia, J.; Agranovich, B.; Shulman, M.; Milman, H.; Baskin, P.; Eisen, B.; Michele, D.E.; Arad, M.; et al. Bioenergetic and Metabolic Impairments in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Duchenne Muscular Dystrophy Patients. Int. J. Mol. Sci. 2022, 23, 9808. https://doi.org/10.3390/ijms23179808
Willi L, Abramovich I, Fernandez-Garcia J, Agranovich B, Shulman M, Milman H, Baskin P, Eisen B, Michele DE, Arad M, et al. Bioenergetic and Metabolic Impairments in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Duchenne Muscular Dystrophy Patients. International Journal of Molecular Sciences. 2022; 23(17):9808. https://doi.org/10.3390/ijms23179808
Chicago/Turabian StyleWilli, Lubna, Ifat Abramovich, Jonatan Fernandez-Garcia, Bella Agranovich, Margarita Shulman, Helena Milman, Polina Baskin, Binyamin Eisen, Daniel E. Michele, Michael Arad, and et al. 2022. "Bioenergetic and Metabolic Impairments in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Duchenne Muscular Dystrophy Patients" International Journal of Molecular Sciences 23, no. 17: 9808. https://doi.org/10.3390/ijms23179808