Mitochondria

Human cardiac mitochondria

We have the following information available:


Model content update:

Dan Beard has pointed out a charge imbalance (of 0.06 [units]) in the mitochondrial Complex IV reaction. The current form of the reaction:

(4) focytC[m] + (7.92) h[m] + o2[m] --> (4) ficytC[m] + (4) h[c] + (1.96) h2o[m] + (0.02) o2s[m]

The above reaction can be replaced with the following 3 reactions:

(4) focytC[m] + (8) h[m] + o2[m] --> (4) ficytC[m] + (4) h[c] + (2) h2o[m]

[m] : focytC --> e- + ficytC

[m] : e- + o2 --> o2s

This set of reactions are charge balanced and have stoichiometric integer coefficients. The downside to this is that superoxide generation is decoupled from the cytochrome c oxidase reaction, thus in order to produce any superoxide in the model, one needs to adjust the flux constraints of the second and/or third reactions. e- refers to electrons (these are not in the model in any other reactions, hence another row would need to be added to the stoichiometric matrix). An alternative to adding an extra row to the stoichiometric matrix would be to simply lump the second and third reactions:

[m] : focytC + o2 --> ficytC + o2s

Additionally it should be noted that the electroneutral form of the phosphate transport reaction (for cytoplasm <==> mitochondria transport and extracellular <==> cytoplasm transport) should be written as as:

(2) h[c] + pi[c] <==> (2) h[m] + pi[m]

as opposed to:

h[c] + pi[c] <==> h[m] + pi[m]

The model building and revision processes are iterative and we appreciate the use of our models by other groups and value any feedback you have to offer - please keep the comments coming!


Vo, T.D., Greenberg, H.J., and Palsson, B.Ø. "Reconstruction and functional characterization of the human mitrochondrial metabolic network based on proteomic and biochemical data" Journal of Biological Chemistry, 2004.

Thiele, I., Price, N.D., Vo, T.D. and Palsson, B.Ø, "Candidate metabolic network states in human mitochondria: Impact of diabetes, ischemia, and diet" Journal of Biological Chemistry, 2004.

If you have any questions about computational modeling of the mitochondria, please email us at ithiele@ucsd.edu

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