Restoring de novo coenzyme Q biosynthesis in Caenorhabditis elegans coq-3 mutants yields profound rescue compared to exogenous coenzyme Q supplementation.
Restoring de novo coenzyme Q biosynthesis in Caenorhabditis elegans coq-3 mutants yields profound rescue compared to exogenous coenzyme Q supplementation.
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DOI：
10.1016/j.gene.2012.06.023
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发表时间：
2012-09-10
期刊：
影响因子：
3.5
通讯作者：
Clarke CF
中科院分区：
文献类型：
--
作者：
Gomez F;Saiki R;Chin R;Srinivasan C;Clarke CF
Coenzyme Q (ubiquinone or Q) is an essential lipid component of the mitochondrial electron transport chain. In Caenorhabditis elegans Q biosynthesis involves at least nine steps, including the hydroxylation of the hydroquinone ring by CLK-1 and two O-methylation steps mediated by COQ-3. We characterize two C. elegans coq-3 deletion mutants, and show that while each has defects in Q synthesis, their phenotypes are distinct. First generation homozygous coq-3(ok506) mutants are fertile when fed the standard lab diet of Q-replete OP50 E. coli, but their second generation homozygous progeny do not reproduce. In contrast, the coq-3(qm188) deletion mutant remains sterile when fed Q-replete OP50. Quantitative PCR analyses suggest that the longer qm188 deletion may alter expression of the flanking nuo-3 and gdi-1 genes, located 5′ and 3′, respectively of coq-3 within an operon. We surmise that variable expression of nuo-3, a subunit of complex I, or of gdi-1, a guanine nucleotide dissociation inhibitor, may act in combination with defects in Q biosynthesis to produce a more severe phenotype. The phenotypes of both coq-3 mutants are more drastic as compared to the C. elegans clk-1 mutants. When fed OP50, clk-1 mutants reproduce for many generations, but show reduced fertility, slow behaviors, and enhanced life span. The coq-3 and clk-1 mutants all show arrested development and are sterile when fed the Q-deficient E. coli strain GD1 (harboring a mutation in the ubiG gene). However, unlike clk-1 mutant worms, neither coq-3 mutant strain responded to dietary supplementation with purified exogenous Q10. Here we show that the Q9 content can be determined in lipid extracts from just 200 individual worms, enabling the determination of Q content in the coq-3 mutants unable to reproduce. An extra-chromosomal array expressing wild-type C. elegans coq-3 rescued fertility of both coq-3 mutants and partially restored steady-state levels of COQ-3 polypeptide and Q9 content, indicating that primary defect in both is limited to coq-3. The limited response of the coq-3 mutants to dietary supplementation with Q provides a powerful model to probe the effectiveness of exogenous Q supplementation as compared to restoration of de novo Q biosynthesis.
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DOI：
10.1083/jcb.111.3.817
发表时间：
1990-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Pauli D;Tonka CH;Tissieres A;Arrigo AP
通讯作者：
Arrigo AP
影响因子：
11.1
作者：
Falk, Marni J.;Polyak, Erzsebet;Zhang, Zhe;Peng, Min;King, Rhonda;Maltzman, Jonathan S.;Okwuego, Ezinne;Horyn, Oksana;Nakamaru-Ogiso, Eiko;Ostrovsky, Julian;Xie, Letian X.;Chen, Jia Yan;Marbois, Beth;Nissim, Itzhak;Clarke, Catherine F.;Gasser, David L.
通讯作者：
Gasser, David L.
影响因子：
4.8
作者：
Marbois, Beth;Xie, Letian X.;Clarke, Catherine F.
通讯作者：
Clarke, Catherine F.
影响因子：
4.8
作者：
Jonassen, T;Clarke, CF
通讯作者：
Clarke, CF
影响因子：
2.9
作者：
Hsu, AY;Poon, WW;Clarke, CF
通讯作者：
Clarke, CF