Nucleic Acids Research Advance Access originally published online on January 30, 2009
Nucleic Acids Research 2009 37(6):1817-1828; doi:10.1093/nar/gkp018
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2009, Vol. 37, No. 6 1817-1828
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development
1Department of Laboratory Medicine, Division of Metabolic Diseases, Novum, Karolinska Institutet, Stockholm SE-141 86, Sweden, 2Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, D-50674 Cologne, Germany, 3Department of Biosciences and Nutrition, Karolinska Institutet & School of Life Sciences, Södertörns Högskola, Huddinge, SE-141 89, Sweden, 4Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, 77030, USA and 5Max Planck Institute for the Biology of Ageing, Köln, Germany
*To whom correspondence should be addressed. Tel: +46 8 5858 3677; Fax: +46 8 779 5383; Email: aleksandra.trifunovic{at}ki.se
Received November 24, 2008. Revised December 29, 2008. Accepted January 7, 2009.
A number of studies showed that the development and the lifespan of Caenorhabditis elegans is dependent on mitochondrial function. In this study, we addressed the role of mitochondrial DNA levels and mtDNA maintenance in development of C. elegans by analyzing deletion mutants for mitochondrial polymerase gamma (polg-1(ok1548)). Surprisingly, even though previous studies in other model organisms showed necessity of polymerase gamma for embryonic development, homozygous polg-1(ok1548) mutants had normal development and reached adulthood without any morphological defects. However, polg-1 deficient animals have a seriously compromised gonadal function as a result of severe mitochondrial depletion, leading to sterility and shortened lifespan. Our results indicate that the gonad is the primary site of mtDNA replication, whilst the mtDNA of adult somatic tissues mainly stems from the developing embryo. Furthermore, we show that the mtDNA copy number shows great plasticity as it can be almost tripled as a response to the environmental stimuli. Finally, we show that the mtDNA copy number is an essential limiting factor for the worm development and therefore, a number of mechanisms set to maintain mtDNA levels exist, ensuring a normal development of C. elegans even in the absence of the mitochondrial replicase.