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Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development.

Bratic I, Hench J, Henriksson J, Antebi A, Bürglin TR, Trifunovic A - Nucleic Acids Res. (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Division of Metabolic Diseases, Novum, Karolinska Institutet, Stockholm SE-141 86, Sweden.

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.

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Mitochondrial morphology in the body wall muscle of (A) control (myo-3::MTS::GFP) and (B) polg-1 deficient (polg-1(ok1548),myo-3::MTS::GFP) adult hermaphrodite animals. (C) Distribution of different mitochondrial lengths “+” stands for polg-1(ok1548) animals and “°” stands for N2 animals.
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Figure 2: Mitochondrial morphology in the body wall muscle of (A) control (myo-3::MTS::GFP) and (B) polg-1 deficient (polg-1(ok1548),myo-3::MTS::GFP) adult hermaphrodite animals. (C) Distribution of different mitochondrial lengths “+” stands for polg-1(ok1548) animals and “°” stands for N2 animals.

Mentions: High mtDNA depletion as observed in adult polg-1 deficient worms may lead to mitochondrial dysfunction, predominantly observed in the high energy demanding, postmitotic tissues, e.g. muscle. Using a muscle-specific GFP fusion gene (myo-3::MTS::GFP) that targets mitochondria in live worms, we observed marked changes in the mitochondrial morphology of polg-1(ok1548) worms (Figure 2B). In control worms, the muscle mitochondria were well organized, running in parallel with the body axis (Figure 2A). In polg-1 deficient worms, the mitochondria were noticeably disorganized and fused (Figure 2B). After quantification of the mitochondrial length we verified that polg-1(ok1548) animals have a much higher incidence of long mitochondria than wild-type worms (Figure 2C). We propose that this increased mitochondrial fusion could be an adaptive response to the mtDNA depletion, allowing functional complementation of mtDNA-encoded proteins.Figure 2.


Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development.

Bratic I, Hench J, Henriksson J, Antebi A, Bürglin TR, Trifunovic A - Nucleic Acids Res. (2009)

Mitochondrial morphology in the body wall muscle of (A) control (myo-3::MTS::GFP) and (B) polg-1 deficient (polg-1(ok1548),myo-3::MTS::GFP) adult hermaphrodite animals. (C) Distribution of different mitochondrial lengths “+” stands for polg-1(ok1548) animals and “°” stands for N2 animals.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2665216&req=5

Figure 2: Mitochondrial morphology in the body wall muscle of (A) control (myo-3::MTS::GFP) and (B) polg-1 deficient (polg-1(ok1548),myo-3::MTS::GFP) adult hermaphrodite animals. (C) Distribution of different mitochondrial lengths “+” stands for polg-1(ok1548) animals and “°” stands for N2 animals.
Mentions: High mtDNA depletion as observed in adult polg-1 deficient worms may lead to mitochondrial dysfunction, predominantly observed in the high energy demanding, postmitotic tissues, e.g. muscle. Using a muscle-specific GFP fusion gene (myo-3::MTS::GFP) that targets mitochondria in live worms, we observed marked changes in the mitochondrial morphology of polg-1(ok1548) worms (Figure 2B). In control worms, the muscle mitochondria were well organized, running in parallel with the body axis (Figure 2A). In polg-1 deficient worms, the mitochondria were noticeably disorganized and fused (Figure 2B). After quantification of the mitochondrial length we verified that polg-1(ok1548) animals have a much higher incidence of long mitochondria than wild-type worms (Figure 2C). We propose that this increased mitochondrial fusion could be an adaptive response to the mtDNA depletion, allowing functional complementation of mtDNA-encoded proteins.Figure 2.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Division of Metabolic Diseases, Novum, Karolinska Institutet, Stockholm SE-141 86, Sweden.

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.

Show MeSH
Related in: MedlinePlus