期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 10, 期 4, 页码 1500-1513出版社
MDPI
DOI: 10.3390/ijms10041500
关键词
Mitochondrial computational model; mitochondrial energetics; excitation-contraction coupling; calcium dynamics; metabolic control analysis; distributed control; control by diffuse loops
资金
- National Institutes of Health [P01HL081427, R33HL87345]
The pattern of flux and concentration control coefficients in an integrated mitochondrial energetics model is examined by applying a generalized matrix method of control analysis to calculate control coefficients, as well as response coefficients The computational model of Cortassa et al. encompasses oxidative phosphorylation, the TCA cycle, and Ca2+ dynamics. Control of ATP synthesis, TCA cycle, and ANT fluxes were found to be distributed among various mitochondrial processes. Control is shared by processes associated with ATP/ADP production and transport, as well as by Ca2+ dynamics. The calculation also analyzed the control of the concentrations of key regulatory ions and metabolites (Ca2+, NADH, ADP). The approach we have used demonstrates how properties of integrated systems may be understood through applications of computational modeling and control analysis.
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