National Institute of Advanced Industrial Science & Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan.
Curr Pharm Des. 2013;19(3):418-29.
Mortalin is a member of Hsp70 family of stress chaperones. It was first identified as a protein involved in the senescence of mouse cells. Genetic studies revealed that there are two mouse mortalin alleles coding for two proteins (mot-1 and mot-2) that differ in only two amino acids in the carboxy-terminus, but have contrasting activities. Whereas mot-1 accelerated senescence, mot-2 extended the lifespan of mouse cells in culture. In human cells, only one kind of mortalin protein has been identified so far and is shown to be functionally equivalent to mouse mot-2. Whereas mortalin is enriched in cancer cells and contributes to carcinogenesis, the old age brain disorders show its deficiency. As we demystify its deux de machina, accumulating evidence reveal that mortalin may be "druggable" bidirectionally to either treat cancer or neuro-degenerative disorders.
线粒体蛋白是热休克蛋白 70 家族的一员，属于应激伴侣。它最初被鉴定为一种参与小鼠细胞衰老的蛋白。遗传研究表明，有两种小鼠线粒体蛋白等位基因编码两种蛋白（mot-1 和 mot-2），它们在羧基末端仅相差两个氨基酸，但具有相反的活性。Mot-1 加速了衰老，而 mot-2 则延长了培养中的小鼠细胞的寿命。在人类细胞中，目前只鉴定出一种线粒体蛋白，其功能与小鼠 mot-2 相当。线粒体蛋白在癌细胞中富集，并有助于致癌作用，而老年期大脑紊乱则显示其缺乏。随着我们揭开它的神秘面纱，越来越多的证据表明，线粒体蛋白可能具有双向“可用药性”，既可以治疗癌症，也可以治疗神经退行性疾病。
