Monoamine oxidase enzymes contribute to mitochondrial oxidant stress and methamphetamine-induced neurodegeneration

Here, Bruker presents research from Dr. Steven Graves. Dr. Steven Graves is interested in investigating the pathogenesis of neurodegenerative diseases and drug-induced neurotoxicity. More specifically, he explores methamphetamine-induced neurodegeneration and the implications this has for developing neurodegenerative diseases such as Parkinson’s Disease. Methamphetamine increases cytosolic dopamine, which is metabolized by monoamine oxidase (MAO) enzymes. Historically, it was believed that cytosolic dopamine would auto-oxidize into a reactive quinone or be deaminated by MAO enzymes resulting in the generation of free electrons that were thought to contribute to cytosolic hydrogen peroxide production. However, during Dr. Graves’ work with Dr. D. James Surmeier at Northwestern University using multiphoton microscopy, they discovered that the electrons generated by MAO metabolism of dopamine were not released into the cytosol; rather, these electrons were transferred to the mitochondrial intermembrane space, thereby supporting the electron transport chain but also increasing oxidant stress.