Mechanistic modeling of aberrant energy metabolism in human disease

Vineet Sangar, James A. Eddy, Evangelos Simeonidis, Nathan D. Price

Research output: Contribution to journalReview articlepeer-review

Abstract

Dysfunction in energy metabolism-including in pathways localized to the mitochondria-has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these moleular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based (CB) models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages-and also provides a powerful means to integrate and interpret-information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, wereview a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regionsin the cell.

Original languageEnglish (US)
Article numberArticle 404
JournalFrontiers in Physiology
Volume3 OCT
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • Constraint-basedmodels
  • Energymetabolism
  • Fluxbalanceanalysis
  • Mitochondria
  • Systemsbiology
  • Warburgeffect

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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