MtDNA segregation in heteroplasmic tissues is common in vivo and modulated by haplotype differences and developmental stage

Joerg Patrick Burgstaller, Iain G Johnston, Nick S Jones, Jana Albrechtová, Thomas Kolbe, Claus Vogl, Andreas Futschik, Corina Mayrhofer, Dieter Klein, Sonja Sabitzer, Mirjam Blattner, Christian Gülly, Joanna Poulton, Thomas Rülicke, Jaroslav Piálek, Ralf Steinborn, Gottfried Brem

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

The dynamics by which mitochondrial DNA (mtDNA) evolves within organisms are still poorly understood, despite the fact that inheritance and proliferation of mutated mtDNA cause fatal and incurable diseases. When two mtDNA haplotypes are present in a cell, it is usually assumed that segregation (the proliferation of one haplotype over another) is negligible. We challenge this assumption by showing that segregation depends on the genetic distance between haplotypes. We provide evidence by creating four mouse models containing mtDNA haplotype pairs of varying diversity. We find tissue-specific segregation in all models over a wide range of tissues. Key findings are segregation in postmitotic tissues (important for disease models) and segregation covering all developmental stages from prenatal to old age. We identify four dynamic regimes of mtDNA segregation. Our findings suggest potential complications for therapies in human populations: we propose "haplotype matching" as an approach to avoid these issues.

Original languageEnglish
Pages (from-to)2031-41
Number of pages11
JournalCell Reports
Volume7
Issue number6
DOIs
Publication statusPublished - 26 Jun 2014

Keywords

  • Amino Acid Sequence
  • Animals
  • DNA, Mitochondrial
  • Disease Models, Animal
  • Haplotypes
  • Humans
  • Mice
  • Models, Genetic
  • Molecular Sequence Data

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