Dr. Kristal began his lecture examining different targets and model systems used to explore the effects of oxidative stresses on mitochondrial function. This included the use of permeability transition, mitochondrial systems sensitive to oxidative stress, mitochondrial transcription and oxidation of specific mitochondrial macromolecules. Dr. Kristal then moved to investigating mitochondrial defense and antioxidant capacity. Addition of redox active compounds and modulation of these defense systems will have a significant impact on the progression of several pathological states. The use of technologies such as small molecule array, proteomics, transgenics and small molecule therapeutics may be the future in this field.
Nitric oxide appears to have multiple effects in the mitochondria.
Not only does NO and NO compounds directly inhibit complexes of the electron transport chain, but NO may compete with oxygen to limit O2 consumption in the cell. Respiration can even be inhibited in nearby cells. Dr. Brown also presented data demonstrating the differential effect of NO on necrosis and apoptosis. NO may induce necrosis, whereas with sufficient glucose and ATP stores, NO may induce apoptosis. Dr. Brown's data supports the hypothesis that there exists a complex interaction between NO, mitochondria and cell death.