MITOsym®

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MITOsym® is a mathematical model similar to DILIsym® software, executed in MATLAB with code and graphical interface versions provided.  Unlike DILIsym®, MITOsym® is a model of mitochondrial function in the in vitro setting, designed to help with parameter identification and data interpretation from experiments conducted to infer mitochondrial function using the Seahorse Bioscience XF Analyzer machines. Ideally, experiments are run on the XF Analyzer machine, data is interpreted and parameters identified with the MITOsym® modeling software, and those parameters are then fed into DILIsym® for in vivo extrapolation.

MITOsym® version 1A featured simulations of mitochondria function and hepatocellular bioenergetics in cultured HepG2 cells, cellular oxygen consumption rate (OCR), cellular extracellular acidification rate (ECAR), ATP levels, and changes in mitochondria proton gradient (ΔΨm).  MITOsym® version 2A expanded upon 1A by adding parameterization for primary rat and human hepatocytes. MITOsym® v2B included the ability to simulate inhibition of glycolysis, as well as reductions in ECAR in presence of compounds. MITOsym® v3A, released in July 2016, includes 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® v5A.