Submit to Cells Review for Cells Propose a Special Issue

Journal Browser

► Journal Browser

Mitochondria Meet Iron Metabolism: Facts and Opportunities

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 16504

Share This Special Issue

Special Issue Editors

Prof. Dr. Francesco Costanzo

E-Mail Website
Guest Editor

Università degli studi Magna Graecia di Catanzaro, Catanzaro, Italy
Interests: iron metabolism; ferritin genes; cancer

Prof. Dr. Flavia Biamonte

E-Mail Website
Guest Editor

Department of Clinical and Experimental Medicine, Magna Græcia University of Catanzaro, Catanzaro, Italy
Interests: iron metabolism; mitochondria bioenergetics; ferroptosis; cancer; cancer therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

iron fulfills a central role in many essential biochemical processes in human physiology; therefore, iron metabolism is a balancing act, and biological systems have evolved exquisite regulatory mechanisms to maintain iron homeostasis.

As major producers of reactive oxygen species (ROS) and focal hubs of iron metabolism, mitochondria are particularly prone to oxidative damage. A positive feedback loop of mitochondrial dysfunction, iron accumulation, and ROS production accounts for the ferroptosis in various neurodegenerative diseases, such as Alzheimer's disease, Huntington Disease, Friedreich's ataxia, and Parkinson's disease, in which these features are present. Alteration in the mitochondrial iron metabolism enables cancer cells to meet the metabolic demands required during different stages of tumorigenesis in relation to metastasis and immune response. Furthermore, mitochondrial iron dysregulation has been linked with different heart conditions, from cardiac ischemia (iron overload) to advanced heart failure (iron deficiency). Mitochondria are also sensitive to iron overload, which has been observed during cardiotoxicity caused by doxorubicin (DOX) and I/R injury.

Iron metabolism constitutes a promising and largely unexploited therapeutic target for the development of new pharmacological treatments for these diseases. Depleting intracellular iron stores, either with the use of iron chelating agents or mimicking endogenous regulation mechanisms, such as microRNAs, present attractive therapeutic opportunities, some of which are currently under clinical investigation. Alternatively, iron overload can result in a form of regulated cell death, which can be activated in cancer cells, presenting an alternative anti-cancer strategy.

The aim of this Special Issue is to assemble original research articles and reviews illustrating how mitochondria are integrated into the system of iron homeostasis in mammalian cells. The articles should focus on the cellular and molecular mechanisms altering mitochondrial iron metabolism during health and disease. Furthermore, this Special Issue aims to provide clinical and experimental evidence on how such mechanisms may be translated into therapy and combined therapeutic approaches.

All scientists working in these fields are cordially invited to submit their manuscripts.

Prof. Dr. Francesco Costanzo
Dr. Flavia Biamonte
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

mitochondria
iron metabolism
cell death
ferroptosis
cancer
neurodegenerative diseases
heart disease

Published Papers (4 papers)

Download All Papers

Research

Jump to: Review

12 pages, 3609 KiB

Open AccessArticle

Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction

by Taeyeon Hong, Jiyeon Ham, Jisoo Song, Gwonhwa Song and Whasun Lim

Cells 2021, 10(2), 332; https://doi.org/10.3390/cells10020332 - 05 Feb 2021

Cited by 18 | Viewed by 2475

Abstract

Brassinin is a phytochemical derived from Chinese cabbage, a cruciferous vegetable. Brassinin has shown anticancer effects on prostate and colon cancer cells, among others. However, its mechanisms and effects on hepatocellular carcinoma (HCC) have not been elucidated yet. Our results confirmed that brassinin exerted antiproliferative effects by reducing proliferating cell nuclear antigen (PCNA) activity, a proliferation indicator and inducing cell cycle arrest in human HCC (Huh7 and Hep3B) cells. Brassinin also increased mitochondrial Ca²⁺ levels and depolarized the mitochondrial membrane in both Huh7 and Hep3B cells. Moreover, brassinin generated high amounts of reactive oxygen species (ROS) in both cell lines. The ROS scavenger N-acetyl-L-cysteine (NAC) inhibited this brassinin-induced ROS production. Brassinin also regulated the AKT and mitogen-activated protein kinases (MAPK) signaling pathways in Huh7 and Hep3B cells. Furthermore, co-administering brassinin and pharmacological inhibitors for JNK, ERK1/2 and P38 decreased cell proliferation in both HCC cell lines more than the pharmacological inhibitors alone. Collectively, our results demonstrated that brassinin exerts antiproliferative effects via mitochondrial dysfunction and MAPK pathway regulation on HCC cells. Full article

(This article belongs to the Special Issue Mitochondria Meet Iron Metabolism: Facts and Opportunities)

► Show Figures

Figure 1

Review

Jump to: Research

17 pages, 1634 KiB

Open AccessReview

Moving beyond the Tip of the Iceberg: DJ-1 Implications in Cancer Metabolism

by Erika Olivo, Marina La Chimia, Jessica Ceramella, Alessia Catalano, Ferdinando Chiaradonna, Maria Stefania Sinicropi, Giovanni Cuda, Domenico Iacopetta and Domenica Scumaci

Cells 2022, 11(9), 1432; https://doi.org/10.3390/cells11091432 - 23 Apr 2022

Cited by 7 | Viewed by 2982

Abstract

DJ-1, also called Parkinson’s protein 7 (PARK7), is ubiquitously expressed and plays multiple actions in different physiological and, especially, pathophysiological processes, as evidenced by its identification in neurodegenerative diseases and its high expression in different types of cancer. To date, the exact activity of DJ-1 in carcinogenesis has not been fully elucidated, however several recent studies disclosed its involvement in regulating fundamental pathways involved in cancer onset, development, and metastatization. At this purpose, we have dissected the role of DJ-1 in maintaining the transformed phenotype, survival, drug resistance, metastasis formation, and differentiation in cancer cells. Moreover, we have discussed the role of DJ-1 in controlling the redox status in cancer cells, along with the ability to attenuate reactive oxygen species (ROS)-dependent cell death, as well as to mediate ferropotosis. Finally, a mention to the development of therapeutic strategies targeting DJ-1 has been done. We have reported the most recent studies, aiming to shed light on the role played by DJ-1 in different cancer aspects and create the foundation for moving beyond the tip of the iceberg. Full article

(This article belongs to the Special Issue Mitochondria Meet Iron Metabolism: Facts and Opportunities)

► Show Figures

Figure 1

26 pages, 1464 KiB

Open AccessFeature PaperReview

Down the Iron Path: Mitochondrial Iron Homeostasis and Beyond

by Jonathan V. Dietz, Jennifer L. Fox and Oleh Khalimonchuk

Cells 2021, 10(9), 2198; https://doi.org/10.3390/cells10092198 - 25 Aug 2021

Cited by 30 | Viewed by 6742

Abstract

Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent. Mitochondria must import iron to form iron–sulfur clusters and heme, and to incorporate these cofactors along with iron ions into mitochondrial proteins that support essential functions, including cellular respiration. In turn, mitochondria supply the cell with heme and enable the biogenesis of cytosolic and nuclear proteins containing iron–sulfur clusters. Impairment in cellular or mitochondrial iron homeostasis is deleterious and can result in numerous human diseases. Due to its reactivity, iron is stored and trafficked through the body, intracellularly, and within mitochondria via carefully orchestrated processes. Here, we focus on describing the processes of and components involved in mitochondrial iron trafficking and storage, as well as mitochondrial iron–sulfur cluster biogenesis and heme biosynthesis. Recent findings and the most pressing topics for future research are highlighted. Full article

(This article belongs to the Special Issue Mitochondria Meet Iron Metabolism: Facts and Opportunities)

► Show Figures

Figure 1

14 pages, 859 KiB

Open AccessReview

Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions

by Sonia Levi, Maddalena Ripamonti, Marko Dardi, Anna Cozzi and Paolo Santambrogio

Cells 2021, 10(8), 1969; https://doi.org/10.3390/cells10081969 - 03 Aug 2021

Cited by 17 | Viewed by 3323

Abstract

In 2001, a new type of human ferritin was identified by searching for homologous sequences to H-ferritin in the human genome. After the demonstration that this ferritin is located specifically in the mitochondrion, it was called mitochondrial ferritin. Studies on the properties of this new type of ferritin have been limited by its very high homology with the cytosolic H-ferritin, which is expressed at higher levels in cells. This great similarity made it difficult to obtain specific antibodies against the mitochondrial ferritin devoid of cross-reactivity with cytosolic ferritin. Thus, the knowledge of the physiological role of mitochondrial ferritin is still incomplete despite 20 years of research. In this review, we summarize the literature on mitochondrial ferritin expression regulation and its physical and biochemical properties, with particular attention paid to the differences with cytosolic ferritin and its role in physiological condition. Until now, there has been no evidence that the alteration of the mitochondrial ferritin gene is causative of any disorder; however, the identified association of the mitochondrial ferritin with some disorders is discussed. Full article

(This article belongs to the Special Issue Mitochondria Meet Iron Metabolism: Facts and Opportunities)

► Show Figures