Artika I Made
Department of Biochemistry, Faculty of Mathematics and Natural Sciences, Bogor Agricultural University, Darmaga Campus, Bogor 16680, Indonesia.
Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia.
Genes Dis. 2019 Aug 31;7(4):578-584. doi: 10.1016/j.gendis.2019.08.001. eCollection 2020 Dec.
Allotopic expression of mitochondrial genes is a deliberate functional relocation of mitochondrial genes into the nucleus followed by import of the gene-encoded polypeptide from the cytoplasm into the mitochondria. For successful allotopic expression of a mitochondrial gene, several key aspects must be considered. These include the different codon dictionary used by the mitochondrial and nuclear genomes, different codon preferences between mitochondrial and nuclear-cytosolic translation systems, and the provision of an import signal to ensure that the newly translated protein in the cytosol is successfully imported into mitochondria. The allotopic expression strategy was first developed in yeast, a useful model organism for studying human and other eukaryotic cells. Currently, a number of mitochondrial genes have been successfully recoded and nuclearly expressed in yeast and human cells. In addition to its use in evolutionary and molecular biology studies, the allotopic expression strategy has been developed as a potential approach to treat mitochondrial genetic disorders. Substantial progress has been recently achieved, and the development of this technique for therapy of the mitochondrial disease Leber's hereditary optic neuropathy (LHON) has entered phase III clinical trials. However, a number of challenges remain to be overcome to accelerate the successful application of this technique. These include improvement of nuclear gene expression, import into mitochondria, processing, and functional integration of the allotopically expressed polypeptides into mitochondrial protein complexes. This review discusses the current basic strategy, progress, challenges, and prospects of the allotopic expression strategy for mitochondrial genes.
线粒体基因的异位表达是将线粒体基因有意地功能性转移到细胞核中，随后将基因编码的多肽从细胞质导入线粒体。为了成功实现线粒体基因的异位表达，必须考虑几个关键方面。这些方面包括线粒体基因组和核基因组使用的不同密码子字典、线粒体和核 - 细胞质翻译系统之间不同的密码子偏好，以及提供一个导入信号以确保细胞质中新翻译的蛋白质成功导入线粒体。异位表达策略最初是在酵母中开发的，酵母是研究人类和其他真核细胞的有用模式生物。目前，许多线粒体基因已在酵母和人类细胞中成功重新编码并在细胞核中表达。除了用于进化和分子生物学研究外，异位表达策略已被开发为一种治疗线粒体遗传疾病的潜在方法。最近已取得了重大进展，该技术用于治疗线粒体疾病Leber遗传性视神经病变（LHON）已进入III期临床试验。然而，要加速该技术的成功应用仍有许多挑战需要克服。这些挑战包括改善核基因表达、导入线粒体、加工以及将异位表达的多肽功能性整合到线粒体蛋白复合物中。本综述讨论了线粒体基因异位表达策略的当前基本策略、进展、挑战和前景。
