Mitochondria and the success of somatic cell nuclear transfer cloning: from nuclear-mitochondrial interactions to mitochondrial complementation and mitochondrial DNA recombination.
The overall success of somatic cell nuclear transfer (SCNT) cloning is rather unsatisfactory, both in terms of efficacy and from an animal health and welfare point of view. Most research activities have concentrated on epigenetic reprogramming problems as one major cause of SCNT failure. The present review addresses the limited success of mammalian SCNT from yet another viewpoint, the mitochondrial perspective. Mitochondria have a broad range of critical functions in cellular energy supply, cell signalling and programmed cell death and, thus, affect embryonic and fetal development, suggesting that inadequate or perturbed mitochondrial functions may adversely affect SCNT success. A survey of perinatal clinical data from human subjects with deficient mitochondrial respiratory chain activity has revealed a plethora of phenotypes that have striking similarities with abnormalities commonly encountered in SCNT fetuses and offspring. We discuss the limited experimental data on nuclear-mitochondrial interaction effects in SCNT and explore the potential effects in the context of new findings about the biology of mitochondria. These include mitochondrial fusion/fission, mitochondrial complementation and mitochondrial DNA recombination, processes that are likely to be affected by and impact on SCNT cloning. Furthermore, we indicate pathways that could link epigenetic reprogramming and mitochondria effects in SCNT and address questions and perspectives for future research.
Hiendleder
Stefan
S
Institute of Molecular Animal Breeding and Biotechnology, Gene Center of the Ludwig-Maximilian University, D-81377 Munich, Germany. s.hiendleder@gen.vetmed.uni-muenchen.de
Zakhartchenko
Valeri
V
Wolf
Eckhard
E
D000818:Animals; D002467:Cell Nucleus / Q000502:physiology*; D019976:Cloning, Organism / Q000379:methods*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D053652:Nuclear Transfer Techniques; D011995:Recombination, Genetic / Q000235:genetics*; D014183:Transplantation, Heterologous
D004272:DNA, Mitochondrial