Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
Centre of New Technologies, University of Warsaw, Warsaw, Poland.
Life Sci Alliance. 2022 Oct 25;6(1). doi: 10.26508/lsa.202201514. Print 2023 Jan.
Most mitochondrial proteins are encoded by nuclear genes, synthetized in the cytosol and targeted into the organelle. To characterize the spatial organization of mitochondrial gene products in zebrafish (), we sequenced RNA from different cellular fractions. Our results confirmed the presence of nuclear-encoded mRNAs in the mitochondrial fraction, which in unperturbed conditions, are mainly transcripts encoding large proteins with specific properties, like transmembrane domains. To further explore the principles of mitochondrial protein compartmentalization in zebrafish, we quantified the transcriptomic changes for each subcellular fraction triggered by the mutation, causing the disorders in the mitochondrial protein import. Our results indicate that the proteostatic stress further restricts the population of transcripts on the mitochondrial surface, allowing only the largest and the most evolutionary conserved proteins to be synthetized there. We also show that many nuclear-encoded mitochondrial transcripts translated by the cytosolic ribosomes stay resistant to the global translation shutdown. Thus, vertebrates, in contrast to yeast, are not likely to use localized translation to facilitate synthesis of mitochondrial proteins under proteostatic stress conditions.
大多数线粒体蛋白由核基因编码,在细胞质中合成,并靶向细胞器。为了描述斑马鱼中线粒体基因产物的空间组织(),我们从不同的细胞部分测序了 RNA。我们的结果证实了核编码 mRNA 存在于线粒体部分,在未受干扰的情况下,这些 mRNA 主要是编码具有特殊性质的大型蛋白的转录本,如跨膜结构域。为了进一步探索斑马鱼中线粒体蛋白区室化的原理,我们量化了每个亚细胞部分在 突变触发下的转录组变化,该突变导致线粒体蛋白导入障碍。我们的结果表明,在蛋白质稳态应激下,进一步限制了位于线粒体表面的转录本的数量,只允许最大和最进化保守的蛋白质在那里合成。我们还表明,许多由细胞质核糖体翻译的核编码线粒体转录本对全局翻译关闭具有抗性。因此,与酵母不同,脊椎动物不太可能在蛋白质稳态应激条件下利用局部翻译来促进线粒体蛋白的合成。