Brain Mitochondria: Pro-Apoptotic Changes After Toxin Exposure

Mitochondria normally function to provide sources of energy for vital cellular functions; however, under stressful conditions these organelles may trigger events that lead eventually to cell death. Thus, mitochondria have been implicated as major contributors to neuronal death in a variety of neurodegenerative disorders. This (University of Miami) report describes functional changes in mitochondria measured in living brain tissue as a result of exposure to toxins thought to contribute to neurodegeneration. Mitochondrial NADH levels are shown to increase following treatment with 1-methyl-4-phenylpyridium (MPP ) at times when neuronal electrophysiology is impaired. In addition, MPP appears to cause oxidation of cytochrome b, providing further support that this toxin inhibits mitochondrial complex I. 3-nitropropionic acid (3-NP) also results in the blockade of neuronal electrical activity, but has minimal effects on mitochondrial NADH and redox activity of respiratory chain cytochromes. Both toxins produce delayed and selective cell death in hippocampal subfield CAl. Neurons in this subfield were previously shown to be selectively vulnerable to hypoxia/ischemia. The reported data suggest that these neurons may also be selectively vulnerable to mitochondrial toxins.