Mitochondrial dynamics controlled by mitofusins define organelle positioning and movement during mouse oocyte maturation
Mitochondrial dynamics controlled by mitofusins define organelle positioning and movement during mouse oocyte maturation
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DOI：
10.1093/molehr/gau064
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发表时间：
2014-11-01
影响因子：
4
通讯作者：
Kono, Tomohiro
中科院分区：
文献类型：
--
作者：
Wakai, Takuya;Harada, Yuichirou;Kono, Tomohiro
线粒体是丰富的完全发育的哺乳动物卵母细胞具有独特的球形形态，但控制线粒体行为的机制还没有很好地理解。在这里，我们描述了第一次在小鼠卵母细胞的线粒体行为的融合/分裂机制的控制。线粒体融合蛋白（Mfn 1和Mfn 2）和OPA 1蛋白分别是线粒体外膜和内膜融合所需的，而Drp 1是线粒体分裂的关键调节因子。我们发现，小鼠卵母细胞表达Mfn 1，Mfn 2，Opa 1和Drp 1蛋白，在未成熟和成熟的卵母细胞在相似的水平。Mfn 1或Mfn 2的过表达引起显著的线粒体聚集，特别是在减数分裂进行期间的核周区域。跟踪线粒体与染色体或内质网（ER）在整个卵母细胞成熟表明，Mfn 1和Mfn 2促进线粒体聚集扰乱时空动态的染色体和ER，分别。我们的研究结果表明，细胞器动力学协调控制在减数分裂，线粒体融合/裂变的不平衡导致解体的细胞器隔间。
Mitochondria are abundant in fully grown mammalian oocytes with a unique spherical morphology, but the mechanisms controlling mitochondria behavior are not well understood. Here we describe for the first time the control of mitochondrial behavior in mouse oocytes by a fusion/fission mechanism. Mitofusins (Mfn1 and Mfn2) and OPA1 proteins are required for outer and inner mitochondrial membrane fusion, respectively, whereas Drp1 is the key regulator of mitochondrial fission. We show that mouse oocytes express the Mfn1, Mfn2, Opa1 and Drp1 proteins, both in immature and mature oocytes at similar levels. Overexpression of Mfn1 or Mfn2 causes marked mitochondrial aggregation, particularly in the perinuclear region during meiotic progression. Tracking of mitochondria with chromosomes or endoplasmic reticulum (ER) throughout oocyte maturation demonstrates that Mfn1 and Mfn2-promoted mitochondrial aggregation disturbs the spatiotemporal dynamic of the chromosomes and ER, respectively. Our findings suggest that organelle dynamics are co-ordinately controlled during meiotic division, and an imbalance of mitochondrial fusion/fission leads to disorganization of the organelle compartments.