Abstract
Accumulation of mitochondrial DNA (mtDNA) mutations appears to be causatively linked to mitochondrial disorders. However, given the complex genetics guiding mtDNA inheritance, the link between a specific mtDNA mutation and the ensuing clinical phenotype is not always clear. In cells, mitochondrial and cellular functions are intricately linked at the level of (energy) metabolism, signal transduction and apoptosis induction. Although mtDNA mutations generally induce malfunctioning of the oxidative phosphorylation (OXPHOS) system, it is currently unclear how mtDNA mutations induce cell dysfunction. Information about the latter is important to complement the biochemical characterization of mtDNA-linked diseases and thereby aid for the rational design of therapeutic strategies. Complex I (NADH:ubiquinone oxidoreductase) is the first complex of the OXPHOS system. This chapter first provides a brief summary of mtDNA genetics in mammals, mtDNA mutations and their clinical phenotype, complex I structure and function and mtDNA-encoded mutations in complex I. Then, an overview is given of the current knowledge concerning the cell biological consequences of pathological mtDNA-encoded mutations in complex I.
Original language | English |
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Title of host publication | A Structural Perspective on Respiratory Complex I |
Subtitle of host publication | Structure and Function of NADH: Ubiquinone Oxidoreductase |
Publisher | Springer |
Pages | 171-189 |
Number of pages | 19 |
ISBN (Electronic) | 9789400741386 |
ISBN (Print) | 9789400741379 |
DOIs | |
Publication status | Published - 1 Jan 2012 |
Externally published | Yes |
Keywords
- ATP
- Cell pathology
- LHON
- mtDNA mutation
- OXPHOS
- Reactive oxygen species