Multiparametric screening

Many mitochondrial functions are associated with the integrity of mitochondrial membranes (inner and outer) and with the exchanges which occur between the outside of the mitochondria, the intermembrane space and the matrix. The mechanisms by which mitochondria can be impaired by drugs mainly concern the following parameters:           

• matrix swelling as a result of the permeabilization of the mitochondrial membranes (usually due to permeability transition pore (PTP) opening),
• alteration of mitochondrial transmembrane potential (ΔΨm),
• release of the cytochrome c from the mitochondria, which reflects the outer membrane permeabilization (Bax/Bak pore, PTP opening),
• inhibition of oxygen consumption or respiratory chain complexes reflecting mitochondrial functionality (oxidative phosphorylation) alteration,
• production of reactive oxygen species (ROS),
• diminution of ATP production,
• alteration of the mitochondrial DNA.