MITOsym is a specialized computer software that functions as a mathematical model, serving as companion software to DILIsym. It is primarily used in the fields of pharmaceutical, medical, and preclinical research for modeling cellular responses to drugs or chemicals. The software is focused on representing the in vitro experimental assessment of mitochondrial function. It allows researchers to replicate experimental conditions and simulate observed mitochondrial dysfunction using identified mechanisms. The software frequently processes data from experimental assessments, such as those conducted with Seahorse Bioscience XF Analyzer machines. This data typically includes measurements like baseline oxygen consumption rate (OCR), the OCR bioenergetic profile (often referred to as the “stress test”), the extracellular acidification rate (ECAR), and the respiratory reserve. By evaluating Seahorse data, researchers can characterize the mechanism (e.g., inhibition of the electron transport chain) by which a compound induces mitochondrial dysfunction. MITOsym facilitates parameter optimization to align simulation results with experimental data, thereby identifying specific parameter values for the mechanism. These MITOsym parameter values, reflecting the in vitro setting, can then be translated to corresponding DILIsym parameter values, which reflect the in vivo setting, providing a comprehensive view from cellular to organismal levels.

Features & Benefits

• MITOsym Version 1A Capabilities
  • Featured simulations of mitochondria function and hepatocellular bioenergetics in cultured HepG2 cells, including cellular oxygen consumption rate (OCR), cellular extracellular acidification rate (ECAR), ATP levels, and changes in mitochondria proton gradient (ΔΨm).
• MITOsym Version 2A Enhancements
  • Expanded upon Version 1A by adding parameterization for primary rat and human hepatocytes.
• MITOsym Version 2B Additions
  • Included the ability to simulate inhibition of glycolysis, as well as reductions in ECAR in the presence of compounds.
• MITOsym Version 3A Features
  • Introduced an electron transport chain (ETC) parameter option that allows for dual effects of an ETC inhibitor (e.g., saturable inhibition at low concentrations, with more marked effects at higher concentrations). This parameter option is mirrored in DILIsym v7A.