title: Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, Division of Metabolic Diseases, Novum, Karolinska Institutet, Stockholm SE-141 86, Sweden.
authors.forename: Ivana
authors.initials: I
authors.lastname: Bratic
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hench
authors.forename: Johan
authors.initials: J
authors.lastname: Henriksson
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bürglin
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Trifunovic
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000254:growth & development; D000074002:DNA Polymerase gamma; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000032:analysis / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000502:physiology*; D006066:Gonads / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D008136:Longevity; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure; D010507:Periodicity; D010641:Phenotype; D012313:RNA / Q000032:analysis; D000077278:RNA, Mitochondrial; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012313:RNA; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase