Cellular consequences of mtDNA-encoded mutations in NADH: Ubiquinone oxidoreductase

Mina Pellegrini, Jan A.M. Smeitink, Peter H.G.M. Willems*, Werner J.H. Koopman

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

1 Citation (Scopus)

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 languageEnglish
Title of host publicationA Structural Perspective on Respiratory Complex I
Subtitle of host publicationStructure and Function of NADH: Ubiquinone Oxidoreductase
PublisherSpringer
Pages171-189
Number of pages19
ISBN (Electronic)9789400741386
ISBN (Print)9789400741379
DOIs
Publication statusPublished - 1 Jan 2012
Externally publishedYes

Keywords

  • ATP
  • Cell pathology
  • LHON
  • mtDNA mutation
  • OXPHOS
  • Reactive oxygen species

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