Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres.

@article{Shimizu2019HemeER,
  title={Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres.},
  author={Toru Shimizu and Alzbeta Lengalova and V{\'a}clav Mart{\'i}nek and Mark{\'e}ta Mart{\'i}nkov{\'a}},
  journal={Chemical Society reviews},
  year={2019}
}
Protoporphyrin IX iron complex (heme) is an important cofactor for oxygen transfer, oxygen storage, oxygen activation, and electron transfer when bound to the heme proteins hemoglobin, myoglobin, cytochrome P450 and cytochrome c, respectively. In addition to these prototypical heme proteins, there are emergent, critical roles of exchangeable/labile heme in signal transduction. Specifically, it has been shown that association/dissociation of heme to/from heme-responsive sensors regulates… 
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TLDR
The importance of understanding the various roles of heme and the distribution of the different heme pools as they relate to the heme redox state, CO, and heme binding affinities is stressed.

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TLDR
It is demonstrated that the N-terminal domain of CdpA is a NosP domain capable of heme binding, which consequently inhibits the c-di-GMP hydrolysis activity of the C-terminals of the phosphodiesterase domain.

Heme inhibits the activity of a c-di-GMP phosphodiesterase in Vibrio cholerae.

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TLDR
This review has attempted to describe how the heme synthesis machinery is regulated by mitochondrial homeostasis as a means of coupling heME synthesis to its utilization and to the metabolic requirements of the cell.

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TLDR
The hematopoietic transcription factor GATA1 induces heme accumulation during erythropoiesis by directly activating genes mediating heme biosynthesis, which leads to a paradigm in which cell type-specific transcriptional mechanisms determine the expression of enzymes mediating the synthesis of small molecules, which generate feedback loops, converging upon the transcription factor itself and the genome.

Understanding the Logistics for the Distribution of Heme in Cells

TLDR
Recent information on the quantification of heme in cells is summarized, and a discussion of a mechanistic framework that could meet the logistical challenge ofHeme distribution is presented.

Crosstalk between Heme Oxygenase-1 and Iron Metabolism in Macrophages: Implications for the Modulation of Inflammation and Immunity

TLDR
Changes in intracellular iron levels play important roles in the regulation of cellular oxidation reactions as well as in the transcriptional and translational regulation of the expression of proteins related to inflammation and immune responses, and therefore, iron metabolism represents a potential target for the development of novel therapeutic strategies focused on the modulation of immunity and inflammation.

Unravelling the mechanisms controlling heme supply and demand

TLDR
It is shown that the cell exhibits exquisite control over release of heme by limiting its availability to one molecule or less within cellular compartments, and an exchange mechanism between protein partners to control supply and demand is suggested.

One ring to bring them all and in the darkness bind them: The Trafficking of Heme without Deliverers.

Heme in Cardiovascular Diseases: A Ubiquitous Dangerous Molecule Worthy of Vigilance

TLDR
The underlying mechanisms by which heme contributes to the development of cardiovascular diseases through oxidative stress, relative pathway gene expression regulation and phenotypic changes in cells are summarized.
...

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