title: Caenorhabditis elegans neuron degeneration and mitochondrial suppression caused by selected environmental chemicals.
abstract: Mitochondrial alterations have been documented for many years in the brains of Parkinson's disease (PD), a disorder that is characterized by the selective loss of dopamine neurons. Recent studies have demonstrated that Parkinson's disease-associated proteins are either present in mitochondria or translocated into mitochondria in response to stress, further reinforcing the importance of the mitochondrial function in the pathogenesis of Parkinson's disease. Exposure to environmental chemicals such as pesticides and heavy metals has been suggested as risk factors in the development of Parkinson's disease. It has been reported that a number of environmental agents including tobacco smoke and perfluorinated compounds, pesticides, as well as metals (Mn(2+) and Pb(2+)) modulate mitochondrial function. However the exact mechanism of mitochondrial alteration has not been defined in the context of the development and progression of Parkinson's disease. The complexity of the mammalian system has made it difficult to dissect the molecular components involved in the pathogenesis of Parkinson's disease. In the present study we used the nematode Caenorhabditis elegans (C. elegans) model of neuron degeneration and investigated the effect of environmental chemicals on mitochondrial biogenesis and mitochondrial gene regulation. Chronic exposure to low concentration (2 or 4 μM) of pesticide rotenone, resulted in significant loss of dopamine neuron in C. elegans, a classic feature of Parkinson's disease. We then determined if the rotenone-induced neuron degeneration is accompanied by a change in mitochondria biogenesis. Analysis of mitochondrial genomic replication by quantitative PCR showed a dramatic decrease in mitochondrial DNA (mtDNA) copies of rotenone-treated C. elegans compared to control. This decreased mitochondrial biogenesis occurred prior to the development of loss of dopamine neurons, and was persistent. The inhibition of mtDNA replication was also found in C. elegans exposed to another neuron toxicant Mn(2+) at the concentration 50 or 100 mM. We further examined the mitochondrial gene expression and found significant lower level of mitochondrial complex IV subunits COI and COII in C. elegans exposed to rotenone. These results demonstrate that environmental chemicals cause persistent suppression of mitochondrial biogenesis and mitochondrial gene expression, and suggest a critical role of modifying mitochondrial biogenesis in toxicants-induced neuron degeneration in C. elegans model.
authors.affiliation: Department of Environmental Health, School of Public Health, Indiana University Bloomington, IN, USA ; Primetox Technologies Wuhan, China.
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Environmental Health, School of Public Health, Indiana University Bloomington, IN, USA.
authors.forename: Zemin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Environmental Health, School of Public Health, Indiana University Bloomington, IN, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Klaunig
keywords: C. elegans; Caenorhabditis elegans; environmental chemicals; mitochondrial suppression; neuron degeneration