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Three Dimensional Reaction‐diffusion Model Of Interaction Between Mitochondria And Sarcoplasmic Reticulum In Heart Muscle Cells
Author(s) -
Vendelin Marko,
Ramay Hena R,
Birkedal Rikke
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1351-b
Subject(s) - mitochondrion , endoplasmic reticulum , biophysics , diffusion , chemistry , coupling (piping) , myofibril , atp synthase , atpase , electron transport chain , biochemistry , biology , materials science , enzyme , physics , metallurgy , thermodynamics
Functional interaction between mitochondria and surrounding ATPases has been found from the experiments on permeabilized heart muscle fibers. According to our earlier analysis of the acquired kinetic data, such interaction can be induced by relatively local diffusion restrictions in cardiac muscle cells. The specific causes of these restrictions are not known but intracellular structures are speculated to act as diffusion barriers. Based on the proximity of sarcoplasmic reticulum (SR) to mitochondria, we hypothesize that SR not only utilizes ATP but may also act as a diffusion barrier for adenosine phosphates leading to functional coupling between ATPases and mitochondria. The structural proximity is evident from electron microscope images where thin SR tubules form loose network around and between consecutive mitochondria. With a 3D finite‐element model, we attempted to explore SR as the first candidate for diffusion barrier. The geometry for the model was constructed using representative mitochondrial and SR structural organization from confocal microscope images. The reaction‐diffusion model was tracking changes for ADP, ATP and Pi in myoplasm, myofibrils, mitochondrial intermembrane space and in the vicinity of mitochondria and SR. To analyze if SR alone could account for diffusion restriction, we compared the model simulation results with the following set of experimental data: mitochondrial respiration rate dependence on exogenous ADP and ATP; influence of pyruvate kinase and phosphoenolpyruvate additions on respiration; stabilization of respiration rate after addition of 2 mM ATP. The research was supported in part by EU Marie Curie Reintegration Grant.