Experimental relocation of the mitochondrial ATP9 gene to the nucleus reveals forces underlying mitochondrial genome evolution.
Experimental relocation of the mitochondrial ATP9 gene to the nucleus reveals forces underlying mitochondrial genome evolution.
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DOI：
10.1371/journal.pgen.1002876
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
di Rago JP
中科院分区：
文献类型：
--
作者：
Bietenhader M;Martos A;Tetaud E;Aiyar RS;Sellem CH;Kucharczyk R;Clauder-Münster S;Giraud MF;Godard F;Salin B;Sagot I;Gagneur J;Déquard-Chablat M;Contamine V;Hermann-Le Denmat S;Sainsard-Chanet A;Steinmetz LM;di Rago JP
每个真核生物保留的线粒体基因组中只剩下少数基因，这些基因执行基本功能并与严重疾病有关。因此，通过实验将这少数基因重新定位到细胞核中具有治疗和进化意义。为此，人们进行了无数次徒劳的尝试，在所有生物体中总共只有 5 次成功。我们采用了一种新方法来重新定位线粒体基因，该方法利用来自其他生物体的天然核版本。我们在 ATP 合酶的 9/c 亚基上证明了这种方法，通过在酿酒酵母中表达来自鹅足孢菌的 ATP9 基因，首次在任何生物体中成功地重新定位了该基因。这项研究证实了蛋白质结构在线粒体基因转移中的作用：嵌合构建体的表达表明，由于第一跨膜片段的疏水性降低，P. anserina 蛋白质可以正确地导入线粒体中。 ATP9 的核表达虽然允许几乎完全功能性的氧化磷酸化，但扰乱了许多细胞特性，包括细胞形态，并激活热休克反应。总而言之，我们的研究建立了一种线粒体基因同位素表达的新策略，证明了重新定位 ATP9 所需的复杂适应，并指出了该基因在多细胞生物进化过程中仅转移到细胞核的原因。线粒体是细胞能量生产的中心，源自一种古老的α-变形菌。虽然其绝大多数基因在进化过程中已转移到核基因组中，但由于尚不完全清楚的原因，少数基因仍保留在所有线粒体基因组中。为了研究基因转移的进化意义并评估线粒体突变引起的严重疾病的潜在治疗方法，研究人员几十年来一直试图从细胞核中表达这些基因。在这项研究中，我们首次成功地将线粒体基因ATP9重新定位到细胞核。该基因编码一种极其疏水的蛋白质，当重新定位时，将其导入线粒体特别具有挑战性。我们通过用来自另一种真菌物种的天然核版本替换 ATP9 在面包酵母中实现了这一目标。 “混合”线粒体可以有效地产生能量，并且在许多方面与正常线粒体相似，尽管它们在导入和组装外来蛋白质方面存在一些困难。我们的研究结果阐明了成功的线粒体基因转移所需的复杂的细胞和蛋白质结构适应，无论是在进化过程中还是在实验过程中。因此，这项研究深入了解了线粒体基因组的进化和能量产生。
Only a few genes remain in the mitochondrial genome retained by every eukaryotic organism that carry out essential functions and are implicated in severe diseases. Experimentally relocating these few genes to the nucleus therefore has both therapeutic and evolutionary implications. Numerous unproductive attempts have been made to do so, with a total of only 5 successes across all organisms. We have taken a novel approach to relocating mitochondrial genes that utilizes naturally nuclear versions from other organisms. We demonstrate this approach on subunit 9/c of ATP synthase, successfully relocating this gene for the first time in any organism by expressing the ATP9 genes from Podospora anserina in Saccharomyces cerevisiae. This study substantiates the role of protein structure in mitochondrial gene transfer: expression of chimeric constructs reveals that the P. anserina proteins can be correctly imported into mitochondria due to reduced hydrophobicity of the first transmembrane segment. Nuclear expression of ATP9, while permitting almost fully functional oxidative phosphorylation, perturbs many cellular properties, including cellular morphology, and activates the heat shock response. Altogether, our study establishes a novel strategy for allotopic expression of mitochondrial genes, demonstrates the complex adaptations required to relocate ATP9, and indicates a reason that this gene was only transferred to the nucleus during the evolution of multicellular organisms. The mitochondrion, centre of cellular energy production, is derived from an ancient alpha-proteobacterium. While the vast majority of its genes have been transferred to the nuclear genome during evolution, a handful of genes remain in all mitochondrial genomes for reasons that are not fully understood. To investigate the evolutionary implications of gene transfer and evaluate potential treatments for the severe diseases caused by mitochondrial mutations, researchers have been attempting to express these genes from the nucleus for decades. In this study, we successfully relocate the mitochondrial gene ATP9 to the nucleus for the first time. This gene encodes an extremely hydrophobic protein that, when relocated, is particularly challenging to import into mitochondria. We achieve this in baker's yeast by replacing ATP9 with a naturally nuclear version from another fungal species. The “hybrid” mitochondria effectively produce energy and resemble normal mitochondria in many aspects, although they have some difficulty importing and assembling the foreign protein. Our findings elucidate the complex cellular and protein structure adaptations required for successful mitochondrial gene transfer, either during evolution or experimentally. This study thus delivers insight into the evolution of mitochondrial genomes and energy production.
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影响因子：
2.6
作者：
Bokori-Brown, Monika;Holt, Ian J.
通讯作者：
Holt, Ian J.
影响因子：
11.4
作者：
Barrientos, A;Zambrano, A;Tzagoloff, A
通讯作者：
Tzagoloff, A
影响因子：
4.8
作者：
HOUSTEK, J;ANDERSSON, U;CANNON, B
通讯作者：
CANNON, B
DOI：
10.1111/j.1432-1033.1988.tb13976.x
发表时间：
1988-04-05
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
FARRELL, LB;GEARING, DP;NAGLEY, P
通讯作者：
NAGLEY, P
影响因子：
4.8
作者：
Godard, Francois;Tetaud, Emmanuel;di Rago, Jean-Paul
通讯作者：
di Rago, Jean-Paul