MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, CB2 0XY, UK.
School of Chemistry, University of Glasgow, Glasgow, G12 8QQ, UK.
Chembiochem. 2023 Jun 1;24(11):e202200774. doi: 10.1002/cbic.202200774. Epub 2023 May 4.
The targeting of bioactive molecules and probes to mitochondria can be achieved by coupling to the lipophilic triphenyl phosphonium (TPP) cation, which accumulates several hundred-fold within mitochondria in response to the mitochondrial membrane potential (Δψ ). Typically, a simple alkane links the TPP to its "cargo", increasing overall hydrophobicity. As it would be beneficial to enhance the water solubility of mitochondria-targeted compounds we explored the effects of replacing the alkyl linker with a polyethylene glycol (PEG). We found that the use of PEG led to compounds that were readily taken up by isolated mitochondria and by mitochondria inside cells. Within mitochondria the PEG linker greatly decreased adsorption of the TPP constructs to the matrix-facing face of the mitochondrial inner membrane. These findings will allow the distribution of mitochondria-targeted TPP compounds within mitochondria to be fine-tuned.
生物活性分子和探针靶向线粒体可以通过与亲脂性三苯基膦（TPP）阳离子偶联来实现，TPP 阳离子在响应线粒体膜电位（Δψ）时在线粒体中积累数百倍。通常，一个简单的烷烃将 TPP 与其“货物”连接起来，从而增加整体疏水性。为了提高靶向线粒体化合物的水溶性，我们探索了用聚乙二醇（PEG）取代烷基连接物的效果。我们发现，使用 PEG 会导致化合物很容易被分离的线粒体和细胞内的线粒体摄取。在线粒体中，PEG 连接物大大减少了 TPP 结构与线粒体内膜面向基质面的吸附。这些发现将使靶向线粒体的 TPP 化合物在线粒体中的分布能够得到精细调整。
