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Mitochondrial Genetic Manipulation

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Somatic Genome Manipulation

Abstract

Mitochondria are key players in cellular metabolism and energy production. They have their own genetic system. The mitochondrial genome is small and contains a limited number of genes, but its expression is complex and essential for survival. Organelle DNA mutations or rearrangements cause incurable neurodegenerative diseases in humans or cytoplasmic male sterility in plants. Manipulating mitochondrial genetics is thus of particular relevance. Conventional transformation of these organelles was only achieved in a couple of unicellular organisms, but the importance of the issue stimulated the development of a wealth of alternative strategies. These include a variety of approaches aiming to transfer DNA into mitochondria and maintain the transfected genetic information, although the problem of selection markers for mitochondrial transformants remains open in most organisms. Conversely, nuclear expression and mitochondrial trafficking of proteins or RNAs through different targeting and shuttling systems have been widely developed to circumvent the need for regular transformation. A number of these methodologies were reported to be successful, for instance to rescue pathogenic mutations in the mitochondrial genome, others are promising. The challenge in the field is currently to define consensus biotechnological tools.

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Acknowledgments

Collaborations with the laboratories of Y. Konstantinov (SIFIBR, Irkutsk, Russia), R.N. Lightowlers (University of Newcastle, UK), G.G.M. D’Souza (MCPHS, Boston, USA) and J. Barciszewski (IBCH, Poznan, Poland) are kindly acknowledged. Our projects are funded by the French Centre National de la Recherche Scientifique (CNRS, UPR2357), the Université de Strasbourg (UdS), the Agence Nationale de la Recherche (ANR-06-MRAR-037-02, ANR-09-BLAN-0240-01) and the Ministère de la Recherche et de l’Enseignement Supérieur (Investissements d’Avenir/Laboratoire d’Excellence MitoCross).

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Mileshina, D., Niazi, A., Weber-Lotfi, F., Gualberto, J., Dietrich, A. (2015). Mitochondrial Genetic Manipulation. In: Li, XQ., Donnelly, D., Jensen, T. (eds) Somatic Genome Manipulation. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2389-2_13

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