Heme Gazing: Illuminating Eukaryotic Heme Trafficking, Dynamics, and Signaling with Fluorescent Heme Sensors.
Heme Gazing: Illuminating Eukaryotic Heme Trafficking, Dynamics, and Signaling with Fluorescent Heme Sensors.
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DOI：
10.1021/acs.biochem.7b00007
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发表时间：
2017-04-04
期刊：
影响因子：
2.9
通讯作者：
Reddi AR
中科院分区：
文献类型：
--
作者：
Hanna DA;Martinez-Guzman O;Reddi AR
血红素（铁原卟啉IX）是地球上大多数生命所必需的蛋白质辅基和信号分子。所有血红素依赖性过程都需要血红素从合成或摄取位点动态快速动员为存在于几乎每个亚细胞区室中的血红素蛋白。血红素的细胞毒性和疏水性需要仔细控制血红素动员，以减轻这种基本毒素的有害影响。事实上，许多疾病，包括某些癌症，心血管疾病，以及衰老和年龄相关的神经退行性疾病，都与血红素稳态的缺陷有关。然而，介导血红素运输和贩运的分子和机制，以及这些过程的动力学，知之甚少。这在很大程度上是由于缺乏探测细胞血红素的物理工具。在此，我们讨论了最近发展的荧光探针，可以监测和图像动力学不稳定血红素方面的动员和信号的作用。特别是，我们将强调如何血红素凝视与这些工具可以发现新的血红素贩运因素后，被整合与遗传筛选和照亮的浓度，亚细胞分布和动态的不稳定血红素在各种生理环境。总之，监测不稳定的血红素，随着最近的生化和细胞生物学研究表明血红素的某些细胞过程的可逆调节沿着，是挑战我们重新概念化血红素从一个静态的辅因子埋在蛋白质活性位点的动态和移动的信号分子。
Heme (iron protoporphyrin IX) is an essential protein prosthetic group and signaling molecule required for most life on Earth. All heme-dependent processes require the dynamic and rapid mobilization of heme from sites of synthesis or uptake to hemoproteins present in virtually every subcellular compartment. The cytotoxicity and hydrophobicity of heme necessitate that heme mobilization be carefully controlled to mitigate the deleterious effects of this essential toxin. Indeed, a number of disorders, including certain cancers, cardiovascular diseases, and aging and age-related neurodegenerative diseases, are tied to defects in heme homeostasis. However, the molecules and mechanisms that mediate heme transport and trafficking, and the dynamics of these processes, are poorly understood. This is in large part due to the lack of physical tools for probing cellular heme. Herein, we discuss the recent development of fluorescent probes that can monitor and image kinetically labile heme with respect to its mobilization and role in signaling. In particular, we will highlight how heme gazing with these tools can uncover new heme trafficking factors upon being integrated with genetic screens and illuminate the concentration, subcellular distribution, and dynamics of labile heme in various physiological contexts. Altogether, the monitoring of labile heme, along with recent biochemical and cell biological studies demonstrating the reversible regulation of certain cellular processes by heme, is challenging us to reconceptualize heme from being a static cofactor buried in protein active sites to a dynamic and mobile signaling molecule.
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影响因子：
64.5
作者：
Haldar M;Kohyama M;So AY;Kc W;Wu X;Briseño CG;Satpathy AT;Kretzer NM;Arase H;Rajasekaran NS;Wang L;Egawa T;Igarashi K;Baltimore D;Murphy TL;Murphy KM
通讯作者：
Murphy KM
DOI：
10.1073/pnas.1409692111
发表时间：
2014-12-09
影响因子：
11.1
作者：
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通讯作者：
English, Ann M.
DOI：
10.1073/pnas.192585799
发表时间：
2002-11-12
影响因子：
11.1
作者：
Atamna, H;Killilea, DW;Ames, BN
通讯作者：
Ames, BN
DOI：
10.1038/nsb0194-30
发表时间：
1994-01-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
FENG, YQ;SLIGAR, SG;WAND, AJ
通讯作者：
WAND, AJ
DOI：
10.1073/pnas.1114514109
发表时间：
2012-02-07
影响因子：
11.1
作者：
Barr, Ian;Smith, Aaron T.;Guo, Feng
通讯作者：
Guo, Feng