Identifying the effects of reactive oxygen species on mitochondrial dynamics and cytoskeleton stability in dictyostelium discoideum

Abstract

Defects in mitochondrial dynamics, fission, fusion, and motility have been implicated in the pathogenesis of multiple neurodegenerative diseases, including Parkinson’s disease, Alz-heimer’s disease, Huntington’s disease, and Charcot–Marie–Tooth disease. Another key feature of neurodegeneration is the increase in reactive oxygen species (ROS). Previous work has shown that the cytoskeleton, in particular the microtubules, and ROS generated by rotenone significantly regulate mitochondrial dynamics in Dictyostelium discoideum. The goal of this project is to study the effects of ROS on mitochondrial dynamics within our model organism D. discoideum to further under-stand the underlying issues that are the root of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. We chose three likely ROS inducers, cumene hydroperoxide, hy-droxylamine hydrochloride, and Antimycin A. Our work demonstrates that alteration of the micro-tubule cytoskeleton is not required to alter dynamics in response to ROS and there is no easy way to predict how mitochondrial dynamics will be altered based on which ROS generator is used. This research contributes to the better understanding of the cellular mechanisms that induce the patho-genesis of incurable neurodegenerative diseases with the hope that it will translate into developing new and more effective treatments for patients afflicted by them.