Redox Biology

Our medical research library holds 6 studies published in Redox Biology (2014–2025). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 6 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Elsevier, B.V
• Published: 2013 to the present, Netherlands
• Language: English
• ISSN: 2213-2317 (electronic)
• Its record in the NLM Catalog

2020s

• POLR1A inhibits ferroptosis by regulating TFAM-mediated mitophagy and iron homeostasis. T. Zhang, Y. Gao, M. Harhai, et al. 2025;85:103758. PubMed · Publisher · Free full text

  Abstract

  Evasion of programmed cell death (PCD) is a hallmark of cancer, yet the mechanisms underlying resistance to ferroptosis - an iron-dependent form of PCD triggered by excessive lipid peroxidation - remain incompletely understood. Here, we identify a previously unrecognized nucleolar-mitochondrial signaling axis that promotes ferroptosis resistance in pleural mesothelioma (PM) and potentially other cancers. This pathway involves RNA polymerase I (PolI) catalytic subunit A (POLR1A) and mitochondrial transcription factor A (TFAM), which together regulate mitophagy and intracellular iron metabolism to suppress ferroptosis. Mechanistically, POLR1A controls TFAM expression via the transcription factor ATF4, and this POLR1A-ATF4-TFAM axis inhibits mitophagy and limit mitophagy-dependent labile Fe2+ release, thereby preventing Fe2+-driven lipid peroxidation. Disruption of this pathway through POLR1A or TFAM inhibition leads to Fe2+ accumulation and increased sensitivity to ferroptosis inducers (FINs). Notably, CX-5461, a first-in-class RNA PolI inhibitor currently in clinical trials, synergizes with GPX4 blockade to induce ferroptotic cell death both in vitro and in vivo. This therapeutic synergy extends beyond PM, suggesting broader relevance in ferroptosis-resistant cancers. Together, our findings reveal a novel mechanism of ferroptosis evasion and establish a promising combinatorial strategy to overcome therapy resistance in cancer.

  Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.

• Ferroptosis-dependent extracellular vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through loading ferritin. F. Ito, K. Kato, I. Yanatori, et al. 2021;47:102174. PubMed · Publisher · Free full text

  Abstract

  Asbestos-associated diseases remain a social burden worldwide. Our previous studies identified asbestos-induced iron-rich milieu for mesothelial cells with ceaseless macrophage ferroptosis. However, molecular mechanisms how this mutagenic milieu influences mesothelial cells have not been elucidated yet. Here, we propose a novel mechanism that extracellular vesicles (EVs) mediate asbestos-associated mutagenic factors to mesothelial cells. In a mice model of intraperitoneal crocidolite injection, mutagenic milieu highly expressed CD63, an exosomal marker. We then used a GFP-CD63 labeled THP-1 macrophage model exposed to crocidolite/iron, which generated EVs under ferroptotic process. We observed that MeT-5A mesothelial cells can receive and internalize these EVs. Furthermore, we comprehensively analyzed the ferroptosis-dependent EVs (FedEVs) for transported proteins and identified ferritin heavy/light chains as major components. Therefore, we inferred that FedEVs transport iron from ferroptotic macrophages to mesothelial cells. RNA sequencing revealed that the mesothelial cells receiving higher amounts of the FedEVs were mitotic, especially at the S and G2/M phases, by the use of Fucci mesothelial cells. Nuclear 8-hydroxy-2'-deoxyguanosine and γ-H2AX were significantly increased in the recipient mesothelial cells after exposure to FedEVs. Collectively, we here demonstrate a novel mechanism that FedEVs act as a key mutagenic mediator by transporting iron, which contribute to asbestos-induced mesothelial carcinogenesis.

  Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

• Lysosomal nitric oxide determines transition from autophagy to ferroptosis after exposure to plasma-activated Ringer's lactate. L. Jiang, H. Zheng, Q. Lyu, et al. 2021;43:101989. PubMed · Publisher · Free full text

  Abstract

  Non-thermal plasma (NTP), an engineered technology to generate reactive species, induces ferroptosis and/or apoptosis specifically in various-type cancer cells. NTP-activated Ringer's lactate (PAL) is another modality for cancer therapy at preclinical stage. Here we found that PAL induces selective ferroptosis of malignant mesothelioma (MM) cells, where non-targeted metabolome screening identified upregulated citrulline-nitric oxide (.NO) cycle as a PAL target. .NO probe detected biphasic peaks transiently at PAL exposure with time-dependent increase, which was responsible for inducible . NO synthase (iNOS) overexpression through NF-κB activation. .NO and lipid peroxidation occupied lysosomes as a major compartment with increased TFEB expression. Not only ferrostatin-1 but inhibitors for . NO and/or iNOS could suppress this ferroptosis. PAL-induced ferroptosis accompanied autophagic process in the early phase, as demonstrated by an increase in essential amino acids, LC3B-II, p62 and LAMP1, transforming into the later phase with boosted lipid peroxidation. Therefore, .NO-mediated lysosomal impairment is central in PAL-induced ferroptosis.

  Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

• Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and β-catenin induction in mesothelium. F. Ito, I. Yanatori, Y. Maeda, et al. 2020;36:101616. PubMed · Publisher · Free full text

  Abstract

  Asbestos is still a social burden worldwide as a carcinogen causing malignant mesothelioma. Whereas recent studies suggest that local iron reduction is a preventive strategy against carcinogenesis, little is known regarding the cellular and molecular mechanisms surrounding excess iron. Here by differentially using high-risk and low-risk asbestos fibers (crocidolite and anthophyllite, respectively), we identified asbestos-induced mutagenic milieu for mesothelial cells. Rat and cell experiments revealed that phagocytosis of asbestos by macrophages results in their distinctive necrotic death; initially lysosome-depenent cell death and later ferroptosis, which increase intra- and extra-cellular catalytic Fe(II). DNA damage in mesothelial cells, as assessed by 8-hydroxy-2'-deoxyguanosine and γ-H2AX, increased after crocidolite exposure during regeneration accompanied by β-catenin activation. Conversely, β-catenin overexpression in mesothelial cells induced higher intracellular catalytic Fe(II) with increased G2/M cell-cycle fraction, when p16INK4A genomic loci localized more peripherally in the nucleus. Mesothelial cells after challenge of H2O2 under β-catenin overexpression presented low p16INK4A expression with a high incidence of deletion in p16INK4A locus. Thus, crocidolite generated catalytic Fe(II)-rich mutagenic environment for mesothelial cells by necrotizing macrophages with lysosomal cell death and ferroptosis. These results suggest novel molecular strategies to prevent mesothelial carcinogenesis after asbestos exposure.

  Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

2010s

• Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia. Z. Li, L. Jiang, S.H. Chew, et al. 2019;26:101297. PubMed · Publisher · Free full text

  Abstract

  Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of metalloenzymes present in all life kingdoms, equilibrating the reactions among CO2, bicarbonate and H+. CA9, a membrane-associated α-CA, has been a drug target for various cancers. Whereas iron is essential not only for cancer cells but also for all the lives on earth, little is known on the association among hypoxia, iron metabolism, extracellular acidity and redox regulation. Malignant mesothelioma (MM), an aggressive tumor with poor prognosis, is an intriguing model in that asbestos-associated pathogenesis includes excess iron environment during carcinogenesis. Re-analysis of rat asbestos-induced MM model revealed an inverse association between high CA9 expression and survival. Here we used human MMs to identify the molecular events surrounding CA9 from the viewpoint of iron metabolism. CA9 expression was significantly higher in MM cells than in MeT-5A mesothelial cells, which was further amplified under hypoxia (1%O2) with increased catalytic Fe(II). CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL. This expressional pattern was similar to that of erastin-induced ferroptosis in the same cells. Furthermore, we observed mitochondrial fission and enhanced autophagy with increased catalytic Fe(II) in both mitochondria and lysosomes after CA9 inhibition, accompanied by increased peroxides, mitochondrial O2- and lipid peroxidation. The eventual cell death was significantly inhibited by deferoxamine, ferrostatin-1 and Z-VAD-FMK, suggesting a mixed cell death of ferroptosis and apoptosis. Therefore, CA9 plays a role in equilibrating among hypoxia, iron metabolism and redox regulation in MM cells.

  Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

• Peroxiredoxin 3 levels regulate a mitochondrial redox setpoint in malignant mesothelioma cells. B. Cunniff, A.N. Wozniak, P. Sweeney, et al. 2014;3:79-87. PubMed · Publisher · Free full text

  Abstract

  Peroxiredoxin 3 (PRX3), a typical 2-Cys peroxiredoxin located exclusively in the mitochondrial matrix, is the principal peroxidase responsible for metabolizing mitochondrial hydrogen peroxide, a byproduct of cellular respiration originating from the mitochondrial electron transport chain. Mitochondrial oxidants are produced in excess in cancer cells due to oncogenic transformation and metabolic reorganization, and signals through FOXM1 and other redox-responsive factors to support a hyper-proliferative state. Over-expression of PRX3 in cancer cells has been shown to counteract oncogene-induced senescence and support tumor cell growth and survival making PRX3 a credible therapeutic target. Using malignant mesothelioma (MM) cells stably expressing shRNAs to PRX3 we show that decreased expression of PRX3 alters mitochondrial structure, function and cell cycle kinetics. As compared to control cells, knockdown of PRX3 expression increased mitochondrial membrane potential, basal ATP production, oxygen consumption and extracellular acidification rates. shPRX3 MM cells failed to progress through the cell cycle compared to wild type controls, with increased numbers of cells in G2/M phase. Diminished PRX3 expression also induced mitochondrial hyperfusion similar to the DRP1 inhibitor mdivi-1. Cell cycle progression and changes in mitochondrial networking were rescued by transient expression of either catalase or mitochondrial-targeted catalase, indicating high levels of hydrogen peroxide contribute to perturbations in mitochondrial structure and function in shPRX3 MM cells. Our results indicate that PRX3 levels establish a redox set point that permits MM cells to thrive in response to increased levels of mROS, and that perturbing the redox status governed by PRX3 impairs proliferation by altering cell cycle-dependent dynamics between mitochondrial networking and energy metabolism.

  Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

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