The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Rotenone selectively kills serotonergic neurons through a microtubule‐dependent mechanism
Open accessAbstract
As a major co‐morbidity of Parkinson’s disease (PD), depression is associated with the loss of serotonergic neurons. Our recent study has shown that midbrain dopaminergic neurons are particularly vulnerable to microtubule‐depolymerizing agents including rotenone, an environmental toxin linked to PD. Here we show that rotenone also selectively killed serotonergic neurons in midbrain neuronal cultures. Its selective toxicity was significantly decreased by the microtubule‐stabilizing drug taxol and mimicked by microtubule‐depolymerizing agents such as colchicine and nocodazole. Microtubule depolymerization induced by rotenone or colchicine caused vesicle accumulation in the soma and killed serotonergic neurons through a mechanism dependent on serotonin metabolism in the cytosol. Blocking serotonin synthesis or degradation, as well as application of antioxidants, significantly reduced the selective toxicity of rotenone or colchicine. Inhibition of vesicular sequestration of serotonin exerted a selective toxicity on serotonergic neurons that was mitigated by blocking serotonin metabolism. Over‐expression of parkin, a protein‐ubiquitin E3 ligase that strongly binds to microtubules, greatly attenuated the selective toxicity of rotenone or colchicine. The protective effects of parkin were abrogated by its PD‐linked mutations. Together, our results suggest that rotenone and parkin affect the survival of serotonergic neurons by impacting on microtubules in opposing manners.
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The CI inhibitor rotenone destabilizes microtubules, and the CII inhibitor α-TOS as well as the complex III inhibitor antimycin act as BH3 mimetics.
“For example, the CI inhibitor rotenone destabilizes microtubules, 40,41 and the CII inhibitor α-TOS as well as the complex III inhibitor antimycin act as BH3 mimetics.42,43”
From Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation (2015) · cites this paper as [41]
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Kluckova, K., Sticha, M., Cerny, J., Mracek, T., Dong, L., Drahota, Z., Gottlieb, E., Neuzil, J., & Rohlena, J. (2015) · Cell Death & Disease · doi:10.1038/cddis.2015.110 · Cited by 66
Metadata
- Authors
- Ren, Y., & Feng, J.
- Affiliations
- University at Buffalo, State University of New York (US)
- Corresponding author
- Feng, Jian
- ORCID
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-06-03
- Volume
- 103
- Issue
- 1
- Pages
- 303-311
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2094552119
- Cited by
- 65
- References
- 30
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 7 · 2012: 2
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS4172)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- rotenone, serotonergic neurons, microtubule depolymerization, Parkinson's disease, depression, Parkin, colchicine, nocodazole, serotonin metabolism, neurotoxicity, midbrain neurons
- MeSH terms
- Amobarbital, Animals, Cells, Cultured, Colchicine, Mesencephalon, Microtubules, Neurons, Parkinson Disease, Rotenone, Serotonin, Cell Death, Electron Transport Complex I, Ubiquitin-Protein Ligases, Rats
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