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Generation of Reactive Oxygen Species by Mitochondrial Complex I: Implications in Neurodegeneration
- Source :
- Neurochemical Research. 33:2487-2501
- Publication Year :
- 2008
- Publisher :
- Springer Science and Business Media LLC, 2008.
-
Abstract
- Mitochondrial Complex I [NADH Coenzyme Q (CoQ) oxidoreductase] is the least understood of respiratory complexes. In this review we emphasize some novel findings on this enzyme that are of relevance to the pathogenesis of neurodegenerative diseases. Besides CoQ, also oxygen may be an electron acceptor from the enzyme, with generation of superoxide radical in the mitochondrial matrix. The site of superoxide generation is debated: we present evidence based on the rational use of several inhibitors that the one-electron donor to oxygen is an iron-sulphur cluster, presumably N2. On this assumption we present a novel mechanism of electron transfer to the acceptor, CoQ. Complex I is deeply involved in pathological changes, including neurodegeneration. Complex I changes are involved in common neurological diseases of the adult and old ages. Mitochondrial cytopathies due to mutations of either nuclear or mitochondrial DNA may represent a useful model of neurodegeneration. In this review we discuss Parkinson's disease, where the pathogenic involvement of Complex I is better understood; the accumulated evidence on the mode of action of Complex I inhibitors and their effect on oxygen radical generation is discussed in terms of the aetiology and pathogenesis of the disease.
- Subjects :
- chemistry.chemical_classification
Reactive oxygen species
Mitochondrial DNA
Electron Transport Complex I
Superoxide
Neurodegeneration
NEURODEGENERATION
Neurodegenerative Diseases
General Medicine
Mitochondrion
Biology
medicine.disease
Biochemistry
Cellular and Molecular Neuroscience
chemistry.chemical_compound
chemistry
Oxidoreductase
Coenzyme Q – cytochrome c reductase
medicine
Humans
MITOCHONDRIAL COMPLEX I
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 15736903 and 03643190
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Neurochemical Research
- Accession number :
- edsair.doi.dedup.....4fc73ce377d9e946bd6cae83c4207d69