Contents

📒 Saa 2013

Modeling the ATP Production in Mitochondria1

Sciwheel

Introduction

Bertram, Pedersen, Luciani, and Sherman (BPLS) model is the simplification of Magnus and Keizer’s with some refinements introduced by Cortassa, 2003.

  • 4 state variables (NADH, ATP, Ca, ΔΨ)
  • some inaccuracies in the BPLS expressions while transcripting math expressions
    • ANT: adenine nucleotide translocator
    • Uni: calcium uniporter

Methods

The issues are fixed by the authers, hence the enhanced BPLS (eBPLS) model.

  • Glycolysis from fructose-1,6-bisphosphate (FBP), as a parameter to pyruvate dehydrogenase (PDH) rate
  • The same 4 state variable as those of BPLS
  • Normalized (dimensionless) quantities for evaluation of freqency response

Equations

https://user-images.githubusercontent.com/40054455/96985739-62dc3680-1553-11eb-89f6-b608c445445d.png

https://user-images.githubusercontent.com/40054455/96985850-6bcd0800-1553-11eb-8809-54af6a5c7b65.png

https://user-images.githubusercontent.com/40054455/96985884-77b8ca00-1553-11eb-8259-4489cd06749d.png

https://user-images.githubusercontent.com/40054455/96985906-7f786e80-1553-11eb-8cb7-208cb53e393e.png

Parameters

https://user-images.githubusercontent.com/40054455/96986068-b2bafd80-1553-11eb-9edb-a6984c393f85.png

Results

https://user-images.githubusercontent.com/40054455/96986216-ec8c0400-1553-11eb-80f2-99e182563fff.png
Frequency response to oscillating cytosolic calcium with different amplitudes

https://user-images.githubusercontent.com/40054455/96986454-3d9bf800-1554-11eb-97a1-f89a9ca7d03e.png
Frequency response Under different concentrations of FBP

Discussion and conclusion

  • Simplifications from KM model, corrections for BPLS model.
  • The inertia of the system tends to increase considerably for high concentrations of cytosolic calcium and FBP.

My point of view

  • Seems not so physiologically sane for the ATP level dropped to zero sometimes.

  1. Saa A, Siqueira KM. Modeling the ATP production in mitochondria. Bull Math Biol. 2013 Sep;75(9):1636–51. ↩︎