Heme Gazing: Illuminating Eukaryotic Heme Trafficking, Dynamics, and Signaling with Fluorescent Heme Sensors
Models, Molecular
0303 health sciences
Escherichia coli Proteins
Recombinant Fusion Proteins
Green Fluorescent Proteins
Gene Expression
Biological Transport
Heme
Cytochrome b Group
Protein Structure, Secondary
Cell Line
3. Good health
Luminescent Proteins
03 medical and health sciences
Bacterial Proteins
Genes, Reporter
Fluorescence Resonance Energy Transfer
Humans
Fluorescent Dyes
Molecular Chaperones
Signal Transduction
DOI:
10.1021/acs.biochem.7b00007
Publication Date:
2017-03-18T16:08:45Z
AUTHORS (3)
ABSTRACT
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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