Int J Biochem Mol Biol 2013;4(4):191-200
Original Article
Caenorhabditis elegans neuron degeneration and mitochondrial suppression caused by
selected environmental chemicals
Shaoyu Zhou, Zemin Wang, James E Klaunig
Department of Environmental Health, School of Public Health, Indiana University, Bloomington, IN, USA; Primetox Technologies, Wuhan, China
Received September 9, 2013; Accepted October 26, 2013; Epub December 15, 2013; Published December 30, 2013
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 (Mn2+ and Pb2+) 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 Mn2+ 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. (IJBMB1309002).
Keywords: Caenorhabditis elegans, C. elegans, neuron degeneration, mitochondrial suppression, environmental chemicals
Address correspondence to: Dr. Shaoyu Zhou, Department of Environmental Health, School of Public Health, Indiana University, Bloomington,
IN 47408, USA. E-mail: zhous@indiana.edu
Original Article
Caenorhabditis elegans neuron degeneration and mitochondrial suppression caused by
selected environmental chemicals
Shaoyu Zhou, Zemin Wang, James E Klaunig
Department of Environmental Health, School of Public Health, Indiana University, Bloomington, IN, USA; Primetox Technologies, Wuhan, China
Received September 9, 2013; Accepted October 26, 2013; Epub December 15, 2013; Published December 30, 2013
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 (Mn2+ and Pb2+) 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 Mn2+ 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. (IJBMB1309002).
Keywords: Caenorhabditis elegans, C. elegans, neuron degeneration, mitochondrial suppression, environmental chemicals
Address correspondence to: Dr. Shaoyu Zhou, Department of Environmental Health, School of Public Health, Indiana University, Bloomington,
IN 47408, USA. E-mail: zhous@indiana.edu
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