Transition metal catalysis in the mitochondria of living cells.

Transition metal catalysis in the mitochondria of living cells.
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DOI:
10.1038/ncomms12538
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发表时间:
2016-09-07
影响因子:
16.6
通讯作者:
Mascarenas, Jose L.
Mascarenas, Jose L.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tomas-Gamasa, Maria;Martinez-Calvo, Miguel;Couceiro, Jose R.;Mascarenas, Jose L.

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能够促进活细胞内非自然转化的过渡金属催化剂的开发可以为化学和细胞生物学开辟重要的新途径。不幸的是,细胞的复杂性使得将标准的有机金属化学转化为生活环境极其困难。因此,这一领域的进展非常缓慢,许多挑战,包括将活性金属催化剂定位到特定的亚细胞位置或细胞器的可能性,仍有待解决。在这里,我们报告了一种设计的Ru络合物,它优先积累在哺乳动物细胞的线粒体内,同时保持其以生物正交方式与外部底物反应的能力。重要的是,我们证明了亚细胞催化活性可以用于限制荧光团的释放,甚至可以通过将惰性前体局部转化为膜电位的解偶联剂来选择性地改变线粒体的功能。由于电池的复杂性,在保持其活性的同时使过渡金属催化剂本地化是非常具有挑战性的。在这里,作者报告了一种积累在线粒体中的Ru络合物,能够促进荧光团或线粒体解偶联剂的受限释放。
The development of transition metal catalysts capable of promoting non-natural transformations within living cells can open significant new avenues in chemical and cell biology. Unfortunately, the complexity of the cell makes it extremely difficult to translate standard organometallic chemistry to living environments. Therefore, progress in this field has been very slow, and many challenges, including the possibility of localizing active metal catalysts into specific subcellular sites or organelles, remain to be addressed. Herein, we report a designed ruthenium complex that accumulates preferentially inside the mitochondria of mammalian cells, while keeping its ability to react with exogenous substrates in a bioorthogonal way. Importantly, we show that the subcellular catalytic activity can be used for the confined release of fluorophores, and even allows selective functional alterations in the mitochondria by the localized transformation of inert precursors into uncouplers of the membrane potential. Due to the complexity of the cell, getting transition metal catalysts localized while retaining their activity is highly challenging. Here, the authors report a ruthenium complex that accumulates in mitochondria and is capable of promoting the confined release of fluorophores or mitochondrial uncouplers.
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