鉴定限制酵母细胞色素 c 氧化酶 Cox2 亚基异位生成的因素。

IF 3.3 3区 生物学 Genetics Pub Date : 2024-04-16 DOI:10.1093/genetics/iyae058
Felipe Nieto-Panqueva, Miriam Vázquez-Acevedo, Patrice P Hamel, Diego González-Halphen
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引用次数: 0

摘要

线粒体基因可以在核基因组中自然或人为地重新定位,这一过程被称为异位表达,编码细胞色素 c 氧化酶(CcO)亚基 II 的线粒体 cox2 基因就是这种情况。在酵母中,如果 Cox2 亚基在第一跨膜伸展段中带有 W56R 取代,则 cox2 可以异位表达,并能恢复 cox2 缺失突变体的呼吸生长。然而,与野生型酵母相比,Cox2W56R 菌株的生长速率降低,稳态 CcO 水平也较低。在这里,我们研究了过量表达某些候选基因的影响,这些基因被预测为能增强异位 COx2W56R 前体在线粒体中的内化。Cox20、Oxa1和Pse1的过量表达促进了Cox2W56R前体的内化,改善了COX2W56R菌株的呼吸生长。过量生产 TIM22 成分对 Cox2W56R 导入的影响有限,而过量生产 TIM23 相关成分则会产生负面影响。我们通过删除和过表达 MGR2 基因,进一步探讨了 TIM23 易位子中的 Mgr2 亚基在导入过程中的作用。我们的研究结果表明,Mgr2 在调节 TIM23 易位子以正确分拣 Cox2W56R 方面发挥了重要作用。我们提出了一条由同源生产的 Cox2 亚基遵循的生物生成途径,该途径基于 TIM23 易位子的两种不同结构/功能形式 TIM23MOTOR 和 TIM23SORT 的参与,它们必须遵循一种协调和有序的作用模式,才能将 Cox2W56R 以正确的 Nout-Cout 拓扑结构插入线粒体内膜。
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Identification of factors limiting the allotopic production of the Cox2 subunit of yeast cytochrome c oxidase.
Mitochondrial genes can be naturally or artificially relocalized in the nuclear genome in a process known as allotopic expression, such is the case of the mitochondrial cox2 gene, encoding subunit II of cytochrome c oxidase (CcO). In yeast, cox2 can be allotopically expressed and is able to restore respiratory growth of a cox2-null mutant if the Cox2 subunit carries the W56R substitution within the first transmembrane stretch. However, the COX2W56R strain exhibits reduced growth rates and lower steady-state CcO levels when compared to wild-type yeast. Here, we investigated the impact of overexpressing selected candidate genes predicted to enhance internalization of the allotopic Cox2W56R precursor into mitochondria. The overproduction of Cox20, Oxa1, and Pse1 facilitated Cox2W56R precursor internalization, improving the respiratory growth of the COX2W56R strain. Overproducing TIM22 components had a limited effect on Cox2W56R import, while overproducing TIM23-related components showed a negative effect. We further explored the role of the Mgr2 subunit within the TIM23 translocator in the import process by deleting and overexpressing the MGR2 gene. Our findings indicate that Mgr2 is instrumental in modulating the TIM23 translocon to correctly sort Cox2W56R. We propose a biogenesis pathway followed by the allotopically produced Cox2 subunit based on the participation of the two different structural/functional forms of the TIM23 translocon, TIM23MOTOR and TIM23SORT, that must follow a concerted and sequential mode of action to insert Cox2W56R into the inner mitochondrial membrane in the correct Nout-Cout topology.
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来源期刊
Genetics
Genetics 生物-遗传学
CiteScore
6.20
自引率
6.10%
发文量
177
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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