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Effects of Rotenone, a Commonly-Used Organic Pesticide on Mitochondrial Complex 1 Function and Altered Immune Responses

Principal Investigator/Project Leader: 
Department of Project: 
Veterinary & Animal Sciences Dept.
Project Description: 

Mitochondria are cellular organelles which are often referred to as the "powerhouse" of the cell. Their many functions include generating the chemical energy utilized by cells, as well as roles in cell signaling, differentiation, cell growth and even cell death. It has been shown that chronic exposures to organic pesticides such as Rotenone, which inhibits mitochondrial function, can result in pathological conditions such as Parkinson's disease. This is attributed to Rotenone's direct effect on Complex I of the respiratory chain, which is one of the five multimeric enzyme complexes (I-V) that carry out the process of oxidative phosphorylation. Thus, given a direct link between the pesticides and Complex I function, it is highly likely that pesticides can affect the health of agricultural livestock as well as farmers and other individuals exposed to pesticides.

The long term goal of this work is to understand the pathophysiological mechanisms of diseases resulting from Complex I deficiencies, which can be targeted for purposes of developing potential therapeutics. The hypothesis that this proposal will test is that Complex I deficiency leads to differences in immune response, which could provide potential biomarkers for associated pathophysiology. This study utilizes a novel genetic model of partial Complex I deficiency to achieve the objectives of the proposed study. The outcomes of this study are expected to reveal differences in one or more aspects of immune components and will aid in our understanding of how chronic Rotenone exposure may alter immune responses. A clear correlation between altered immune response and Complex I deficiency will provide a potential biomarker for mitochondrial dysfunction-associated pathophysiology, which will be very useful for monitoring the efficacies of therapies to normalize the immune response.