气候变化领域集成服务门户(CCPortal): Unravelling the mechanisms controlling heme supply and demand

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DOI	10.1073/pnas.2104008118
	Unravelling the mechanisms controlling heme supply and demand
	Leung G.C.-H.; Fung S.S.-P.; Gallio A.E.; Blore R.; Alibhai D.; Raven E.L.; Hudson A.J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:22
英文摘要	In addition to heme's role as the prosthetic group buried inside many different proteins that are ubiquitous in biology, there is new evidence that heme has substantive roles in cellular signaling and regulation. This means that heme must be available in locations distant from its place of synthesis (mitochondria) in response to transient cellular demands. A longstanding question has been to establish the mechanisms that control the supply and demand for cellular heme. By fusing a monomeric heme-binding peroxidase (ascorbate peroxidase, mAPX) to a monomeric form of green-fluorescent protein (mEGFP), we have developed a heme sensor (mAPXmEGFP) that can respond to heme availability. By means of fluorescence lifetime imaging, this heme sensor can be used to quantify heme concentrations; values of the mean fluorescence lifetime (τMean) for mAPX-mEGFP are shown to be responsive to changes in free (unbound) heme concentration in cells. The results demonstrate that concentrations are typically limited to one molecule or less within cellular compartments. These miniscule amounts of free heme are consistent with a system that sequesters the heme and is able to buffer changes in heme availability while retaining the capability to mobilize heme when and where it is needed. We propose that this exchangeable supply of heme can operate using mechanisms for heme transfer that are analogous to classical ligand-exchange mechanisms. This exquisite control, in which heme is made available for transfer one molecule at a time, protects the cell against the toxic effect of excess heme and offers a simple mechanism for heme-dependent regulation in single-molecule steps. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Biosensing; Fluorescence lifetime imaging; Heme biology
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238907
作者单位	School of Chemistry, University of Leicester, Leicester, LE1 7RH, United Kingdom; Leicester Institute of Structural & Chemical Biology, University of Leicester, Leicester, LE1 7HB, United Kingdom; School of Chemistry, University of Bristol, Bristol, BS8 1TS, United Kingdom; Wolfson Bioimaging Facility, Faculty of Life Sciences, University of Bristol, Bristol, BS8 1TD, United Kingdom
推荐引用方式 GB/T 7714	Leung G.C.-H.,Fung S.S.-P.,Gallio A.E.,et al. Unravelling the mechanisms controlling heme supply and demand[J],2021,118(22).
APA	Leung G.C.-H..,Fung S.S.-P..,Gallio A.E..,Blore R..,Alibhai D..,...&Hudson A.J..(2021).Unravelling the mechanisms controlling heme supply and demand.Proceedings of the National Academy of Sciences of the United States of America,118(22).
MLA	Leung G.C.-H.,et al."Unravelling the mechanisms controlling heme supply and demand".Proceedings of the National Academy of Sciences of the United States of America 118.22(2021).