نبذة مختصرة : Mitochondria are organelles found in eukaryotic cells. They are involved in many vital cellular functions. Consequently, mitochondrial dysfunction leads to a variety of human disorders. Many studies of the last 50 years showed that mitochondria are involved in the regulation of physiological ageing. However, the underlying mechanisms are still unknown. We aimed to analyze the mitochondrial role in ageing in Caenorhabditis elegans model system. Its short life cycle, powerful genetic tools and known fates of all 959 post-mitotic somatic cells make this nematode an excellent model system for ageing studies. Besides numerous advantages, the small body size of the worm brings along certain technical limitations. We developed a toolkit to analyze mitochondrial morphology, metabolic profile and electron transport chain (ETC) activities on a single-tissue level. In addition, we adapted a method for analysis of mtDNA copy number for use on individual animals. Each mitochondrion has its own genome that is maintained by mitochondrial DNA polymerase gamma (POLG). By analyzing polg-1 mutant worms that are deficient in the sole mitochondrial DNA polymerase, we showed that C. elegans mtDNA replication mainly takes place in the gonad, the only proliferative tissue in adult worms. Thus mtDNA depletion leads to marked dysfunction of this organ. Severe mtDNA depletion leads to embryonic arrest, whereas mild depletion does not affect development. We showed that mtDNA replication does not take place during embryogenesis; it starts during the L3 larval stage, correlating with germline proliferation. Taken together, mtDNA copies in the somatic tissues mainly stem from the oocyte and stay relatively unchanged during development and early adulthood. Remarkably, somatic tissues are not severely affected in polg-1 deficient animals despite the marked overall mtDNA depletion in contrast to other model systems, namely flies and mice. Furthermore, we showed that mtDNA copy number exhibits substantial plasticity upon environmental stress. ...
Relation: I. Caenorhabditis elegans as a model system for mtDNA replication defects. Ivana Bratic, Jürgen Hench, Aleksandra Trifunovic. Methods. 2010, 51:437-443. ::doi::10.1016/j.ymeth.2010.03.003 ::pmid::20230897 ::isi::000281049900012; II. Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development. Ivana Bratic, Jürgen Hench, Johan Henriksson, Adam Antebi, Thomas R Bürglin and Aleksandra Trifunovic. Nucleic Acid Research. 2009, Vol. 37, No.6:1817-1828. ::doi::10.1093/nar/gkp018 ::pmid::19181702 ::isi::000265097400017; III. A tissue-specific approach to the analysis of metabolic changes in Caenorhabditis elegans. Jürgen Hench*, Ivana Bratic Hench*, Claire Pujol, Sabine Ipsen, Susanne Brodesser, Arnaud Mourier, Markus Tolnay, Stephan Frank and Aleksandra Trifunovic. *Authors contributed equally to this work. [Submitted]; IV. Succin ate dehydrogenase divergently regulates longevity in Caenorhabditis elegans mitochondrial mutants. Ivana Bratic Hench, Claire Pujol, Marija Sumakovic, Jürgen Hench, Linda Baumann and Aleksandra Trifunovic. [Manuscript]; http://hdl.handle.net/10616/40663
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