Identification of small molecule modulators of mitochondrial activity using functional assays with purified biological active mitochondria

Mitochondria play crucial roles in living cells. They are not only the source of energy via oxidative phosphorylation and ATP synthesis, but are also important regulators of cellular survival and in the control of programmed cell death. Mitochondrial damage and inhibition of the electron transfer in the respiratory chain can trigger the production of reactive oxygen species (ROS) and the release of cytochrome c. The latter initiates mitochondrial induction of apoptosis. For better understanding of the role of mitochondria in cell proliferation and homeostasis and for the development of drugs targeting specific mitochondrial activities, we investigate bioorganometallic compounds for the specific activity on purified mitochondria. Mitochondria were prepared from mouse liver and a series of tests was established that show mitochondrial functionality. Particular focus is given on mitochondrial respiratory activity measuring oxygen consumption and the capability of various substances to influence respiration and selectively inhibit respiratory chain components in purified mitochondria. Our study revealed that some salophene iron complexes, rhodium (III) polypyridyl complexes and benzimidazol-2-ylidene gold(I) Complexes directly inhibit mitochondrial respiration. Furthermore some bioorganometallic substances trigger the release of cytochrome c and change the mitochondrial membrane potential.

This work is supported by the DFG FOR630.