Natural competence of mammalian mitochondria allows the molecular investigation of mitochondrial gene expression
Natural competence of mammalian mitochondria allows the molecular investigation of mitochondrial gene expression
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DOI：
10.1093/hmg/ddi435
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Lightowlers, RN
中科院分区：
文献类型：
--
作者：
Koulintchenko, M;Temperley, RJ;Lightowlers, RN
呼吸是哺乳动物细胞的一个基本过程，它需要两个基因组，一个是细胞核，一个是线粒体（mtDNA）。mtDNA的突变在疾病中得到越来越多的认识，并可能在衰老过程中发挥重要作用。接受线粒体dna基因产物的重要作用，我们关于线粒体基因表达细节的有限知识是令人惊讶的。这在一定程度上是由于我们无法转染线粒体和操纵它们的基因组。已经有声称成功地将DNA导入分离细胞器，但大多数报道缺乏表达的证据，也没有任何方法进一步加深我们对基因表达的理解。在这里，我们报道哺乳动物线粒体具有天然的DNA导入能力。通过五种功能分析，我们发现进口DNA可以作为DNA合成或启动子驱动转录的模板，由此产生的多顺反子RNA被加工（5‘和3’）并被切除的mt-tRNA成熟。利用这种自然能力将使我们能够探索线粒体基因在细胞器中的表达，并提供线粒体转染在体内的潜力。
Respiration, a fundamental process in mammalian cells, requires two genomes, those of the nucleus and the mitochondrion (mtDNA). Mutations of mtDNA are being increasingly recognized in disease and may play an important role in the ageing process. Accepting the vital role of mtDNA gene products, our limited knowledge concerning the details of mitochondrial gene expression is surprising. This is, in part, due to our inability to transfect mitochondria and to manipulate their genome. There have been claims of successful DNA import into isolated organelles, but most reports lacked evidence of expression and no method has furthered our understanding of gene expression. Here, we report that mammalian mitochondria possess a natural competence for DNA import. Using five functional assays, we show imported DNA can act as templates for DNA synthesis or promoter-driven transcription, with the resultant polycistronic RNA being processed (5' and 3') and excised mt-tRNA matured. Exploiting this natural competence will allow us to explore mitochondrial gene expression in organello and provides the potential for mitochondrial transfection in vivo.