ArticlePLoS computational biology2018
Insights on the impact of mitochondrial organisation on bioenergetics in high-resolution computational models of cardiac cell architecture.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Metabolic fatty acid substrates enhance the structural and mechanical performance of human-induced pluripotent stem cell-derived cardiomyocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Reversing diastolic dysfunction in diabetes: a mitochondrial quality control-centric pharmacological approach.Acta diabetologica · 2026Review
- Estimating physical conditions supporting gradients of ATP concentration in the eukaryotic cell.Biophysical journal · 2026Article
- A transmission electron microscopy platform for assessing mitochondrial and nuclear architecture in cardiomyocytes.Cell reports methods · 2025Article
- Excitation and mechanical contraction of a 3D cardiomyocyte model.Biophysical journal · 2025Article
- Calcium Overload and Mitochondrial Metabolism.Biomolecules · 2022Review
- Effects of altered cellular ultrastructure on energy metabolism in diabetic cardiomyopathy: anPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- Computational Modeling and Imaging of the Intracellular Oxygen Gradient.International journal of molecular sciences · 2022Article
- Mitophagy-regulated mitochondrial health strongly protects the heart against cardiac dysfunction after acute myocardial infarction.Journal of cellular and molecular medicine · 2022Article
- Paradoxes of Hymenoptera flight muscles, extreme machines.Biophysical reviews · 2022Review
- Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.Frontiers in physiology · 2022Review
- Sensing local energetics to acutely regulate mitophagy in skeletal muscle.Frontiers in cell and developmental biology · 2022Review
- Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cell Volume (3D) Correlative Microscopy Facilitated by Intracellular Fluorescent Nanodiamonds as Multi-Modal Probes.Nanomaterials (Basel, Switzerland) · 2020Article
- Impact of global structure on diffusive exploration of organelle networks.Scientific reports · 2020Article
- Computational/Experimental Interrogation of the Failing Heart-A Perspective on "Impaired Myocardial Energetics Causes Mechanical Dysfunction in Decompensated Failing Hearts".Function (Oxford, England) · 2020Article
- Impaired Myocardial Energetics Causes Mechanical Dysfunction in Decompensated Failing Hearts.Function (Oxford, England) · 2020Article
- Precision remodeling: how exercise improves mitochondrial quality in myofibers.Current opinion in physiology · 2019Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent electron microscopy data have revealed that cardiac mitochondria are not arranged in crystalline columns but are organised with several mitochondria aggregated into columns of varying sizes spanning the cell cross-section. This raises the question-how does the mitochondrial arrangement affect the metabolite distributions within cardiomyocytes and what is its impact on force dynamics? Here, we address this question by employing finite element modeling of cardiac bioenergetics on computational meshes derived from electron microscope images. Our results indicate that heterogeneous mitochondrial distributions can lead to significant spatial variation across the cell in concentrations of inorganic phosphate, creatine (Cr) and creatine phosphate (PCr). However, our model predicts that sufficient activity of the creatine kinase (CK) system, coupled with rapid diffusion of Cr and PCr, maintains near uniform ATP and ADP ratios across the cell cross sections. This homogenous distribution of ATP and ADP should also evenly distribute force production and twitch duration with contraction. These results suggest that the PCr shuttle and associated enzymatic reactions act to maintain uniform force dynamics in the cell despite the heterogeneous mitochondrial organization. However, our model also predicts that under hypoxia activity of mitochondrial CK enzymes and diffusion of high-energy phosphate compounds may be insufficient to sustain uniform ATP/ADP distribution and hence force generation.
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