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Metal Transporters in Health and Disease

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Dear Colleagues,

Essential metals, such as zinc, iron and manganese, play a fundamental role in regulating the number of molecules; thus, their abnormal homeostasis causes damage in cells. On the other hand, cadmium and mercury are toxic metals, and cells must therefore control them to avoid cellular impairments.

The homeostasis of these essential and toxic metals is controlled by various transporters and channels. This Special Issue focuses on the recent developments of metal transporters from the perspectives of physiology, toxicology, and pharmacology, with the aim of understanding their biological relevance in human health and diseases, addressing the future directions and questions underlying their unique phenomenon, in particular their potential use as drug targets for human diseases.

Increasing discoveries and questions concerning the pathophysiological contribution of metal transporters highlight the rising attention and interest in this field of research. Therefore, we believe this Special Issue will provide appropriate information about the implications and mechanisms of metal dynamics for health and disease, and thus should appeal to a wide range of readers.

The 33rd Meeting of Japan Society for Biomedical Research on Trance Elements 2022 (BRTE2022, https://brte2022.jimdosite.com) will be held at Awaji-shima, Japan on the 8–10 September 2022. All attendees presenting a paper at this conference are welcome to submit a manuscript for publication. For further information, please contact the Editorial Office.

Prof. Dr. Toshiyuki Fukada
Prof. Dr. Mitchell D. Knutson
Prof. Dr. Moon-Suhn Ryu
Guest Editors

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Keywords

essential trace elements (Fe, Zn, Mn, Cu, Se, etc.)
toxic elements (Cd, Hg, Pb, As, etc.)
transporters
channels
physiology
toxicology
pharmacology
disease

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Research

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14 pages, 3245 KiB

Open AccessArticle

Structure and Function of the Zinc Binding Protein ZrgA from Vibrio cholerae

by Daniel W. Valencia, Ady B. Meléndez, Isaac A. Melendrez and Erik T. Yukl

Int. J. Mol. Sci. 2023, 24(1), 548; https://doi.org/10.3390/ijms24010548 - 29 Dec 2022

Cited by 1 | Viewed by 1646

Abstract

ATP binding cassette (ABC) transporters are the primary means by which bacteria acquire trace elements from the environment. They rely on solute binding proteins (SBPs) to bind the relevant substrate and deliver it to the integral membrane permease for ATP-powered import into the cytoplasm. SBPs of cluster A-I are known to facilitate the transport of essential metals zinc, manganese, and iron, and many have been characterized to date. A group of ABC transporter operons dubbed zinc-regulated genes (zrg) have recently been shown to transport zinc with putative SBPs (zrgA) bearing no homology to the classical cluster A-I family, and a recent crystal structure of a representative protein from Pseudomonas aeruginosa shows no structural similarity to classical SBPs. Thus, the ZrgA proteins appear to represent a newly discovered family of zinc SBPs widespread among Gram-negative bacteria, including human pathogens. Here, we have determined the crystal structure of ZrgA from Vibrio cholerae and characterized its zinc binding in vitro and function in vivo. We also assessed the role of a histidine-rich sequence that appears to be a hallmark of ZrgA proteins that is particularly long in V. cholerae ZrgA. The results show that the zrgA gene is critical to the function of the operon, consistent with a function as an SBP in this system. Further, the His-rich region is not essential to the function of ZrgA, but it does provide additional zinc binding sites in vitro. The structure and zinc binding data for ZrgA reveal interesting differences between it and its homologue from P. aeruginosa, illustrating diversity within this little-studied protein family. Full article

(This article belongs to the Special Issue Metal Transporters in Health and Disease)

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16 pages, 3404 KiB

Open AccessReview

Zinc in Cardiovascular Functions and Diseases: Epidemiology and Molecular Mechanisms for Therapeutic Development

by Takafumi Hara, Emi Yoshigai, Takuto Ohashi and Toshiyuki Fukada

Int. J. Mol. Sci. 2023, 24(8), 7152; https://doi.org/10.3390/ijms24087152 - 12 Apr 2023

Cited by 2 | Viewed by 2418

Abstract

Zinc is an essential trace element that plays an important physiological role in numerous cellular processes. Zinc deficiency can result in diverse symptoms, such as impairment of the immune response, skin disorders, and impairments in cardiovascular functions. Recent reports have demonstrated that zinc acts as a signaling molecule, and its signaling pathways, referred to as zinc signals, are related to the molecular mechanisms of cardiovascular functions. Therefore, comprehensive understanding of the significance of zinc-mediated signaling pathways is vital as a function of zinc as a nutritional component and of its molecular mechanisms and targets. Several basic and clinical studies have reported the relationship between zinc level and the onset and pathology of cardiovascular diseases, which has attracted much attention in recent years. In this review, we summarize the recent findings regarding the effects of zinc on cardiovascular function. We also discuss the importance of maintaining zinc homeostasis in the cardiovascular system and its therapeutic potential as a novel drug target. Full article

(This article belongs to the Special Issue Metal Transporters in Health and Disease)

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