Control and regulation of integrated mitochondrial function in metabolic and transport networks

Sonia Carmen Cortassa, Brian O'Rourke, Raimond L. Winslow, Miguel Antonio Aon

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1500-1513
Number of pages14
JournalInternational journal of molecular sciences
Issue number4
StatePublished - Apr 2009


  • Calcium dynamics
  • Control by diffuse loops
  • Distributed control
  • Excitationcontraction coupling
  • Metabolic control analysis
  • Mitochondrial computational model
  • Mitochondrial energetics

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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