Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10
Abstract
Chronic exposure to the pesticide rotenone induces a selective degeneration of nigrostriatal dopaminergic neurons and reproduces the features of Parkinson's disease in experimental animals. This action is thought to be relevant to its inhibition of the mitochondrial complex I, but the precise mechanism of this suppression in selective neuronal death is still elusive. Here we investigate the mechanism of dopaminergic neuronal death mediated by rotenone in primary rat mesencephalic neurons. Low concentrations of rotenone (5–10 n m) induce the selective death of dopaminergic neurons without significant toxic effects on other mesencephalic cells. This cell death was coincident with apoptotic events including capsase‐3 activation, DNA fragmentation, and mitochondrial membrane depolarization. Pretreatment with coenzyme Q 10, the electron transporter in the mitochondrial respiratory chain, remarkably reduced apoptosis as well as the mitochondrial depolarization induced by rotenone, but other free radical scavengers such as N‐acetylcysteine, glutathione, and vitamin C did not. Furthermore, the selective neurotoxicity of rotenone was mimicked by the mitochondrial protonophore carbonyl cyanide 4‐(trifluoromethoxy) phenylhydrazone (FCCP), a cyanide analog that effectively collapses a mitochondrial membrane potential. These data suggest that mitochondrial depolarization may play a crucial role in rotenone‐induced selective apoptosis in rat primary dopaminergic neurons.
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CoQ10 protects against paraquat and rotenone induced mitochondrial dysfunction and neuronal cell death in human neuroblastoma (SHSY-5Y) cells and primary rat mesencephalic neurons respectively.
“It protects against paraquat and rotenone induced mitochondrial dysfunction and neuronal cell death in human neuroblastoma (SHSY-5Y) cells and primary rat mesencephalic neurons respectively140, 141.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [141]
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- Authors
- Moon, Y., Lee, K. H., Park, J., Geum, D., & Kim, K.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Kim, Kyungjin
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2005-04-26
- Volume
- 93
- Issue
- 5
- Pages
- 1199-1208
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1524718556
- Cited by
- 174
- References
- 58
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 2 · 2023: 10 · 2022: 13 · 2021: 11 · 2020: 7 · 2019: 10 · 2018: 7 · 2017: 8 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 10
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- rotenone, coenzyme Q10, dopaminergic neurons, mitochondrial depolarization, selective neuronal death, apoptosis, Parkinson's disease, mitochondrial complex I inhibition, mesencephalic neurons, FCCP, radical scavengers, caspase-3, DNA fragmentation
- MeSH terms
- Animals, Antioxidants, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Cells, Cultured, Coenzymes, Dopamine, Electrophysiology, Intracellular Membranes, Ionophores, Mesencephalon, Mitochondria, Neurons, Neurotoxins, Rotenone, Ubiquinone, Cell Death, Rats, Sprague-Dawley, Apoptosis, Cytoprotection, Caspases, Rats, Caspase 3
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