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.
|van Waveren, Corina; Moraes, Carlos T (2008) Transcriptional co-expression and co-regulation of genes coding for components of the oxidative phosphorylation system. BMC Genomics 9:18|