Effects of Fcj1-Mos1 and mitochondrial division on aggregation of mitochondrial DNA nucleoids and organelle morphology.
Effects of Fcj1-Mos1 and mitochondrial division on aggregation of mitochondrial DNA nucleoids and organelle morphology.
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DOI：
10.1091/mbc.e13-03-0125
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发表时间：
2013-06
影响因子：
3.3
通讯作者：
Sesaki H
中科院分区：
文献类型：
--
作者：
Itoh K;Tamura Y;Iijima M;Sesaki H
线粒体DNA类核在线粒体内呈离散灶状分布。类核的分布是由线粒体分裂和Fcj 1和Mos 1，两个进化上保守的，线粒体蛋白，维持嵴连接和管状细胞器形态控制。线粒体DNA（mitochondrialDNA，mtDNA）被包装成DNA-蛋白质复合物，称为类核，在线粒体内呈多个小灶状分布。类核对于mtDNA的生物发生和功能至关重要。在这里，使用酵母遗传筛选控制类核分布和大小的组件，我们确定Fcj 1和Mos 1，两个进化上保守的线粒体蛋白，保持嵴和边界膜之间的连接。这两种蛋白质对于建立线粒体的管状形态也很重要，因为缺乏Fcj 1和Mos 1的线粒体形成板层片。我们发现，类核聚集，增加的大小，并减少在fcj 1？？和mos 1？？细胞的数量。此外，Fcj 1形成点状结构并定位于类核附近。此外，通过删除细胞器分裂所需的DNM 1基因来连接线粒体，增强了fcj 1 α和mos 1 β细胞中mtDNA类核的聚集，而DNM 1的单一缺失不影响类核。相反，删除F1 Fo-ATP合酶二聚化因子产生同心环状嵴，恢复管状线粒体形态，并抑制这些突变体中的类核聚集。我们的研究结果表明Fcj 1-Mos 1和细胞器分裂在维持mtDNA类核的分布和大小方面具有意想不到的作用。
Mitochondrial DNA nucleoids are distributed as many discrete foci in mitochondria. Nucleoid distribution is controlled by mitochondrial division and Fcj1 and Mos1, two evolutionarily conserved, mitochondrial proteins that maintain cristae junctions and tubular organelle morphology. Mitochondrial DNA (mtDNA) is packaged into DNA–protein complexes called nucleoids, which are distributed as many small foci in mitochondria. Nucleoids are crucial for the biogenesis and function of mtDNA. Here, using a yeast genetic screen for components that control nucleoid distribution and size, we identify Fcj1 and Mos1, two evolutionarily conserved mitochondrial proteins that maintain the connection between the cristae and boundary membranes. These two proteins are also important for establishing tubular morphology of mitochondria, as mitochondria lacking Fcj1 and Mos1 form lamellar sheets. We find that nucleoids aggregate, increase in size, and decrease in number in fcj1∆ and mos1∆ cells. In addition, Fcj1 form punctate structures and localized adjacent to nucleoids. Moreover, connecting mitochondria by deleting the DNM1 gene required for organelle division enhances aggregation of mtDNA nucleoids in fcj1∆ and mos1∆ cells, whereas single deletion of DNM1 does not affect nucleoids. Conversely, deleting F1Fo-ATP synthase dimerization factors generates concentric ring-like cristae, restores tubular mitochondrial morphology, and suppresses nucleoid aggregation in these mutants. Our findings suggest an unexpected role of Fcj1-Mos1 and organelle division in maintaining the distribution and size of mtDNA nucleoids.