Horton Kristin L, Stewart Kelly M, Fonseca Sonali B, Guo Qian, Kelley Shana O
Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON M5S 3M2, Canada.
Chem Biol. 2008 Apr;15(4):375-82. doi: 10.1016/j.chembiol.2008.03.015.
Mitochondria are important targets for cancer chemotherapy and other disease treatments. Gaining access to this organelle can be difficult, as the inner membrane is a barrier limiting diffusive transport. A mitochondrial molecular carrier would be a boon to the development of organelle-specific therapeutics. Here, we report a significant advance in the development of mitochondrial transporters-synthetic cell-permeable peptides that are able to enter mitochondria. Efficient uptake of these mitochondria-penetrating peptides (MPPs) is observed in a variety of cell types, and organellar specificity is attained with sequences that possess specific chemical properties. The MPPs identified are cationic, but also lipophilic; this combination of characteristics facilitates permeation of the hydrophobic mitochondrial membrane. The examination of a panel of MPPs illustrates that mitochondrial localization can be rationally controlled and finely tuned by altering lipophilicity and charge.
线粒体是癌症化疗和其他疾病治疗的重要靶点。由于内膜是限制扩散运输的屏障，进入这个细胞器可能会很困难。线粒体分子载体将有助于细胞器特异性治疗药物的开发。在这里，我们报告了线粒体转运体——能够进入线粒体的合成细胞穿透肽——开发方面的一项重大进展。在多种细胞类型中都观察到这些线粒体穿透肽（MPP）的有效摄取，并且通过具有特定化学性质的序列实现了细胞器特异性。所鉴定的MPP是阳离子型的，但也是亲脂性的；这种特性组合有助于穿过疏水的线粒体膜。对一组MPP的研究表明，通过改变亲脂性和电荷，可以合理地控制和微调线粒体定位。
