人类线粒体tRNA生物合成与线粒体疾病

Human Mitochondrial tRNA Synthesis and Mitochondrial Diseases

线粒体是普遍存在于真核细胞中的一类细胞器.每个线粒体含有多个拷贝的闭合环状双链DNA.人类线粒体DNA(mitochondrial DNA,mtDNA)共编码22种线粒体tRNA(mitochondrial tRNA,mt tRNA),2种rRNA及13种多肽.mt tRNA独特的结构特点决定了它们与具有典型三叶草结构的细胞质tRNA不同.编码mt tRNA的基因突变频率较高,这可能是引起线粒体功能障碍的主要原因之一.同时,这与很多病理现象相关.目前发现,大量与mt tRNA生物代谢和功能相关的核因子包括加工内切酶、tRNA修饰酶和氨酰-tRNA合成酶.这些核因子的异常导致了疾病相关的tRNA致病突变.由此可见mt tRNA功能对于线粒体活性的重要性.

Mitochondria are membrane-enclosed organelles found in eukaryotic cells to supply adenosine triphosphate （ATP） as the energy molecules. Mitochondrial DNA （mtDNA） is a circular molecule that codes 22 transfer RNAs, two ribosomal RNAs and 13 proteins. Mitochondrial tRNA is different from cytoplasmic tRNA and does not have a typical clover structure. The high-frequency mutations in mitochondrial tRNAs may cause mitochondrial dysfunction. Several nuclear factors, including processing endonuclease, tRNA modification enzymes and aminoaeyl-tRNA synthetase, are involved in the biosynthesis and function of mitochondrial tRNA. Abnormalities of these nuclear factors associated with pathogenic mitochondrial tRNA mutations lead to diseases.