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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Eukaryotic complex I: functional diversity and experimental systems to unravel the assembly process.

With more than 40 subunits, one FMN co-factor and eight FeS clusters, complex I or NADH:ubiquinone oxidoreductase is the largest multimeric respiratory enzyme in the mitochondria. In this review, we focus on the diversity of eukaryotic complex I. We describe the additional activities that have been reported to be associated with mitochondrial complex I and discuss their physiological significance. The recent identification of complex I-like enzymes in the hydrogenosome, a mitochondria-derived organelle is also discussed here. Complex I assembly in the mitochondrial inner membrane is an intricate process that requires the cooperation of the nuclear and mitochondrial genomes. The most prevalent forms of mitochondrial dysfunction in humans are deficiencies in complex I and remarkably, the molecular basis for 60% of complex I-linked defects is currently unknown. This suggests that mutations in yet-to-be-discovered assembly genes should exist. We review the different experimental systems for the study of complex I assembly. To our knowledge, in none of them, large screenings of complex I mutants have been performed. We propose that the unicellular green alga Chlamydomonas reinhardtii is a promising system for such a study. Complex I mutants can be easily scored on a phenotypical basis and a large number of transformants generated by insertional mutagenesis can be screened, which opens the possibility to find new genes involved in the assembly of the enzyme. Moreover, mitochondrial transformation, a recent technological advance, is now available, allowing the manipulation of all five complex I mitochondrial genes in this organism.[1]

References

  1. Eukaryotic complex I: functional diversity and experimental systems to unravel the assembly process. Remacle, C., Barbieri, M.R., Cardol, P., Hamel, P.P. Mol. Genet. Genomics (2008) [Pubmed]
 
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