Danpure C J
MRC Laboratory for Molecular Cell Biology, University College London, UK.
Bioessays. 1997 Apr;19(4):317-26. doi: 10.1002/bies.950190409.
Under the putative influence of dietary selection pressure, the subcellular distribution of alanine:glyoxylate aminotransferase 1 (AGT) has changed on many occasions during the evolution of mammals. Depending on the particular species, AGT can be found either in peroxisomes or mitochondria, or in both peroxisomes and mitochondria. This variable localization depends on the differential expression of N-terminal mitochondrial and C-terminal peroxisomal targeting sequences by the use of alternative transcription and translation initiation sites. AGT is peroxisomal in most humans, but it is mistargeted to the mitochondria in a subset of patients suffering from the rare hereditary disease primary hyperoxaluria type 1. Mistargeting is due to the unlikely combination of a normally occurring polymorphism that generates a functionally weak mitochondrial targeting sequence and a disease-specific mutation which, in combination with the polymorphism, inhibits AGT dimerization. The mechanisms by which AGT can be targeted differentially to peroxisomes and/or mitochondria highlight the different molecular requirements for protein import into these two organelles.
在假定的饮食选择压力影响下，丙氨酸：乙醛酸转氨酶1（AGT）的亚细胞分布在哺乳动物进化过程中多次发生变化。根据特定物种的不同，AGT可存在于过氧化物酶体或线粒体中，或同时存在于过氧化物酶体和线粒体中。这种可变的定位取决于通过使用不同的转录和翻译起始位点，N端线粒体靶向序列和C端过氧化物酶体靶向序列的差异表达。在大多数人类中，AGT存在于过氧化物酶体中，但在患有罕见遗传性疾病1型原发性高草酸尿症的一部分患者中，它被错误定位于线粒体。错误定位是由于一种正常发生的多态性产生了功能较弱的线粒体靶向序列，以及一种疾病特异性突变，该突变与多态性相结合，抑制了AGT二聚化。AGT能够被差异靶向到过氧化物酶体和/或线粒体的机制，突出了蛋白质导入这两个细胞器的不同分子要求。
