EXPLORING NUCLEAR-MITOCHONDRIAL DNA INTERACTIONS

Project: Research project

Project Details

Description

DESCRIPTION (Investigator's abstract): We propose to study
nuclear-mitochondrial interactions by using a collection of cell lines and
embryos harboring the nuclear background from one species and the mitochondrial
genome from a different species. Because oxidative phosphorylation (OXPHOS)
depends on the interaction between these two genomes, which have co-evolved to
optimize energy production, xenomitochondrial cells are commonly deficient in
respiration.

In the last three years we produced human xenomitochondrial cybrids harboring
non-human primate's mitochondrial genomes and used these cell lines as cellular
models of mitochondrial diseases and as tools to study nuclear-mitochondrial
interactions, such as mitochondrial DNA maintenance and copy number control.
Models of respiratory complexes I and IV deficiencies were also obtained
depending on the primate mitochondrial DNA coexisting with the human nuclear
DNA. We now propose to expand these preliminary results to other species and to
better define the mechanisms associated with defective nuclear-mitochondrial
interactions.

We also propose to study mechanisms of mtDNA maintenance in early development.
We will use cross-species cloned embryos and animals produced by nuclear
transfer to assess mtDNA maintenance in a xenomitochondrial environment. We
will also study some physical and biochemical properties of oocyte mitochondria
and test if these specific features are optimized for mitochondrial maintenance
in the egg.
StatusFinished
Effective start/end date5/1/978/31/06

Funding

  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences: $249,525.00
  • National Institute of General Medical Sciences: $271,351.00
  • National Institute of General Medical Sciences: $199,839.00
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences: $237,938.00
  • National Institute of General Medical Sciences: $284,226.00

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