Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3-4
pubmed:dateCreated
2007-2-5
pubmed:abstractText
Mitochondrial Complex I (NADH Coenzyme Q 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 Coenzyme Q (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. Strong evidence is accumulating that electron transfer from Complex I to Complex III via CoQ is not performed by operation of the CoQ pool but by direct channelling within a super-complex including Complex I, Complex III and bound CoQ. Besides structural evidence of a Complex I -Complex III aggregate obtained by native electrophoresis, we have obtained kinetic evidence based on metabolic flux analysis, demonstrating that Complexes I and III behave as an individual enzyme. Quantitative and qualitative changes of phospholipids, including peroxidation, may affect the supercomplex formation. Complex I is deeply involved in pathological changes, including neurodegeneration. Maternally inherited mutations in mitochondrial DNA genes encoding for Complex I subunits are at the basis of Leber's Hereditary Optic Neuropathy; a decrease of electron transfer in the complex, due to the mutations, is not sufficient per se to explain the clinical phenotype, and other factors including proton translocation and oxygen radical generation have been considered of importance. Complex I changes are also involved in more common neurological diseases of the adult and old ages. 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0021-2938
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
232-53
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17274529-Animals, pubmed-meshheading:17274529-Coenzymes, pubmed-meshheading:17274529-Electron Transport, pubmed-meshheading:17274529-Electron Transport Complex I, pubmed-meshheading:17274529-Flavin Mononucleotide, pubmed-meshheading:17274529-Humans, pubmed-meshheading:17274529-Iron-Sulfur Proteins, pubmed-meshheading:17274529-Mitochondrial Myopathies, pubmed-meshheading:17274529-Models, Biological, pubmed-meshheading:17274529-Models, Chemical, pubmed-meshheading:17274529-Multienzyme Complexes, pubmed-meshheading:17274529-Neurodegenerative Diseases, pubmed-meshheading:17274529-Optic Atrophy, Hereditary, Leber, pubmed-meshheading:17274529-Parkinson Disease, pubmed-meshheading:17274529-Protein Structure, Quaternary, pubmed-meshheading:17274529-Proton Pumps, pubmed-meshheading:17274529-Reactive Oxygen Species, pubmed-meshheading:17274529-Ubiquinone
pubmed:articleTitle
Mitochondrial Complex I: structure, function, and implications in neurodegeneration.
pubmed:affiliation
Dipartimento di Biochimica "G. Moruzzi", Università di Bologna, Italy. lenaz@biocfarm.unibo.it
pubmed:publicationType
Journal Article, Review