Ubiquinone is necessary for mouse embryonic development but is not essential for mitochondrial respiration

被引:107
作者
Levavasseur, F
Miyadera, H
Sirois, J
Tremblay, ML
Kita, K
Shoubridge, E
Hekimi, S
机构
[1] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada
[2] Univ Tokyo, Dept Biomed Chem, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan
[3] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
[4] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada
[5] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2B4, Canada
关键词
D O I
10.1074/jbc.M108980200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ubiquinone (UQ) is a lipid found in most biological membranes and is a co-factor in many redox processes including the mitochondrial respiratory chain. UQ has been implicated in protection from oxidative stress and in the aging process. Consequently, it is used as a dietary supplement and to treat mitochondrial diseases. Mutants of the clk-1 gene of the nematode Caenorhabditis elegans are fertile and have an increased life span, although they do not produce UQ but instead accumulate a biosynthetic intermediate, demethoxyubiquinone (DMQ). DMQ appears capable to partially replace UQ for respiration in vivo and in vitro. We have produced a vertebrate model of cells and tissues devoid of UQ by generating a knockout mutation of the murine orthologue of clk-1 (mclk1). We find that mclk1-/- embryonic stem cells and embryos accumulate DMQ instead of UQ. As in the nematode mutant, the activity of the mitochondrial respiratory chain of -/- embryonic stem cells is only mildly affected (65% of wild-type oxygen consumption). However, mclk1-/- embryos arrest development at midgestation, although earlier developmental stages appear normal. These findings indicate that UQ is necessary for vertebrate embryonic development but suggest that mitochondrial respiration is not the function for which UQ is essential when DMQ is present.
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收藏
页码:46160 / 46164
页数:5
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