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Mitochondrial-Localized Versus Cytosolic Intracellular CO-Releasing Organic PhotoCORMs: Evaluation of CO Effects Using Bioenergetics
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2018-06-22 00:00:00 , DOI: 10.1021/acschembio.8b00387
Livia S Lazarus 1 , Hector J Esquer 2 , Stacey N Anderson 1 , Lisa M Berreau 1 , Abby D Benninghoff 2
Affiliation  

While interactions between carbon monoxide (CO) and mitochondria have been previously studied, the methods used to deliver CO (gas or CO-releasing metal carbonyl compounds) lack subcellular targeting and/or controlled delivery. Thus, the effective concentration needed to produce changes in mitochondrial bioenergetics is yet to be fully defined. To evaluate the influence of mitochondrial-targeted versus intracellularly released CO on mitochondrial oxygen consumption rates, we developed and characterized flavonol-based CO donor compounds that differ at their site of release. These molecules are metal-free, visible light triggered CO donors (photoCORMs) that quantitatively release CO and are trackable in cells via confocal microscopy. Our studies indicate that at a concentration of 10 μM, the mitochondrial-localized and cytosolic CO-releasing compounds are similarly effective in terms of decreasing ATP production, maximal respiration, and the reserve capacity of A549 cells. This concentration is the lowest to impart changes in mitochondrial bioenergetics for any CO-releasing molecule (CORM) reported to date. The results reported herein demonstrate the feasibility of using a structurally tunable organic photoCORM framework for comparative intracellular studies of the biological effects of carbon monoxide.

中文翻译:

线粒体定位与胞质内 CO 释放有机 PhotoCORM:利用生物能学评估 CO 效应

虽然之前已经研究过一氧化碳 (CO) 和线粒体之间的相互作用,但用于递送 CO(气体或释放 CO 的金属羰基化合物)的方法缺乏亚细胞靶向和/或受控递送。因此,产生线粒体生物能量变化所需的有效浓度尚未完全确定。为了评估线粒体靶向与细胞内释放的 CO 对线粒体耗氧率的影响,我们开发并表征了基于黄酮醇的 CO 供体化合物,其释放位点不同。这些分子是不含金属的可见光触发 CO 供体 (photoCORM),可定量释放 CO,并可通过共聚焦显微镜在细胞中进行追踪。我们的研究表明,浓度为 10 μM 时,线粒体定位和胞质 CO 释放化合物在减少 ATP 产生、最大呼吸和 A549 细胞的储备能力方面同样有效。对于迄今为止报道的任何 CO 释放分子 (CORM) 来说,该浓度是引起线粒体生物能变化的最低浓度。本文报告的结果证明了使用结构可调的有机 photoCORM 框架进行一氧化碳生物效应的比较细胞内研究的可行性。
更新日期:2018-06-22
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