A simple model of cardiac mitochondrial respiration with experimental validation
Cardiac mitochondria are intracellular organelles that play an important role in energy metabolism and cellular calcium regulation. In particular, they influence the excitation-contraction cycle of the heart cell. A large number of mathematical models have been proposed to better understand the mito...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
AIMS Press
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/6906f08bdff74def8f828220365e6c1b |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:6906f08bdff74def8f828220365e6c1b |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:6906f08bdff74def8f828220365e6c1b2021-11-09T03:01:32ZA simple model of cardiac mitochondrial respiration with experimental validation10.3934/mbe.20212911551-0018https://doaj.org/article/6906f08bdff74def8f828220365e6c1b2021-06-01T00:00:00Zhttps://www.aimspress.com/article/doi/10.3934/mbe.2021291?viewType=HTMLhttps://doaj.org/toc/1551-0018Cardiac mitochondria are intracellular organelles that play an important role in energy metabolism and cellular calcium regulation. In particular, they influence the excitation-contraction cycle of the heart cell. A large number of mathematical models have been proposed to better understand the mitochondrial dynamics, but they generally show a high level of complexity, and their parameters are very hard to fit to experimental data. We derived a model based on historical free energy-transduction principles, and results from the literature. We proposed simple expressions that allow to reduce the number of parameters to a minimum with respect to the mitochondrial behavior of interest for us. The resulting model has thirty-two parameters, which are reduced to twenty-three after a global sensitivity analysis of its expressions based on Sobol indices. We calibrated our model to experimental data that consists of measurements of mitochondrial respiration rates controlled by external ADP additions. A sensitivity analysis of the respiration rates showed that only seven parameters can be identified using these observations. We calibrated them using a genetic algorithm, with five experimental data sets. At last, we used the calibration results to verify the ability of the model to accurately predict the values of a sixth dataset. Results show that our model is able to reproduce both respiration rates of mitochondria and transitions between those states, with very low variability of the parameters between each experiment. The same methodology may apply to recover all the parameters of the model, if corresponding experimental data were available.Bachar Tarraf Emmanuel Suraniti Camille ColinStéphane Arbault Philippe DiolezMichael LeguèbeYves Coudière AIMS Pressarticlebiological modelingmitochondriaordinary differential equationssensitivity analysisexperimental validationBiotechnologyTP248.13-248.65MathematicsQA1-939ENMathematical Biosciences and Engineering, Vol 18, Iss 5, Pp 5758-5789 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
biological modeling mitochondria ordinary differential equations sensitivity analysis experimental validation Biotechnology TP248.13-248.65 Mathematics QA1-939 |
| spellingShingle |
biological modeling mitochondria ordinary differential equations sensitivity analysis experimental validation Biotechnology TP248.13-248.65 Mathematics QA1-939 Bachar Tarraf Emmanuel Suraniti Camille Colin Stéphane Arbault Philippe Diolez Michael Leguèbe Yves Coudière A simple model of cardiac mitochondrial respiration with experimental validation |
| description |
Cardiac mitochondria are intracellular organelles that play an important role in energy metabolism and cellular calcium regulation. In particular, they influence the excitation-contraction cycle of the heart cell. A large number of mathematical models have been proposed to better understand the mitochondrial dynamics, but they generally show a high level of complexity, and their parameters are very hard to fit to experimental data.
We derived a model based on historical free energy-transduction principles, and results from the literature. We proposed simple expressions that allow to reduce the number of parameters to a minimum with respect to the mitochondrial behavior of interest for us. The resulting model has thirty-two parameters, which are reduced to twenty-three after a global sensitivity analysis of its expressions based on Sobol indices.
We calibrated our model to experimental data that consists of measurements of mitochondrial respiration rates controlled by external ADP additions. A sensitivity analysis of the respiration rates showed that only seven parameters can be identified using these observations. We calibrated them using a genetic algorithm, with five experimental data sets. At last, we used the calibration results to verify the ability of the model to accurately predict the values of a sixth dataset.
Results show that our model is able to reproduce both respiration rates of mitochondria and transitions between those states, with very low variability of the parameters between each experiment. The same methodology may apply to recover all the parameters of the model, if corresponding experimental data were available. |
| format |
article |
| author |
Bachar Tarraf Emmanuel Suraniti Camille Colin Stéphane Arbault Philippe Diolez Michael Leguèbe Yves Coudière |
| author_facet |
Bachar Tarraf Emmanuel Suraniti Camille Colin Stéphane Arbault Philippe Diolez Michael Leguèbe Yves Coudière |
| author_sort |
Bachar Tarraf |
| title |
A simple model of cardiac mitochondrial respiration with experimental validation |
| title_short |
A simple model of cardiac mitochondrial respiration with experimental validation |
| title_full |
A simple model of cardiac mitochondrial respiration with experimental validation |
| title_fullStr |
A simple model of cardiac mitochondrial respiration with experimental validation |
| title_full_unstemmed |
A simple model of cardiac mitochondrial respiration with experimental validation |
| title_sort |
simple model of cardiac mitochondrial respiration with experimental validation |
| publisher |
AIMS Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/6906f08bdff74def8f828220365e6c1b |
| work_keys_str_mv |
AT bachartarraf asimplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT emmanuelsuraniti asimplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT camillecolin asimplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT stephanearbault asimplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT philippediolez asimplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT michaelleguebe asimplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT yvescoudiere asimplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT bachartarraf simplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT emmanuelsuraniti simplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT camillecolin simplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT stephanearbault simplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT philippediolez simplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT michaelleguebe simplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation AT yvescoudiere simplemodelofcardiacmitochondrialrespirationwithexperimentalvalidation |
| _version_ |
1718441390017347584 |