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Biomolecules
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Cysteine and Selenocysteine in Antioxidant Defense, Protein Synthesis and Signaling...
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Cysteine and Selenocysteine in Antioxidant Defense, Protein Synthesis and Signaling Pathways

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 3641

Special Issue Editors

Prof. Dr. Maria Wrobel

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Guest Editor
Chair in Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7 Cracow, 3 1-034 Kraków, Poland
Interests: biochemistry; medical biochemistry; tissue-specific expression and function of sulfurtransferases
Special Issues, Collections and Topics in MDPI journals
Dr. Halina Jurkowska

E-Mail Website
Guest Editor
Chair in Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, 31034 Kraków, Poland
Interests: biochemistry; anticancer research; amino acids; pharmacological reports
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will cover aspects on the importance of cysteine and selenocysteine in antioxidant defense, signaling pathways in the aging process, inflammatory responses in neurodegenerative and cardiovascular diseases, diabetes and other diseases, and protein synthesis. The following topics will be covered: mitochondrial redox metabolism; antioxidant and anticancer potential of taurine (product of cysteine oxidation); sulfide signaling; persulfides/polysulfides in the regulation of metabolism; selenoproteins (including glutathione peroxidase and thioredoxin reductase) in redox signaling; selenium-based molecules as catalytic H2S/H2O2 scavengers; metabolism of hydrogen sulfide (H2S, an endogenous gasotransmitter) and hydrogen selenide (H2Se-, the biologically available and active form of selenium, is suggested to be a nitric oxide-like signaling molecule); modulation of expression/activity of enzymes involved in H2S and selenium metabolism: cystathionine β-synthase (EC 4.2.1.22, CBS), cystathionine γ-lyase (EC 4.4.1.1, CTH), 3-mercaptopyruvate sulfurtransferase (EC 2.8.1.2, MST), thiosulfate sulfurtransferase (EC 2.8.1.1, TST, rhodanese), methanethiol oxidase (MTO, EC 1.8.3.4, selenium-binding protein 1), and selenocysteine lyase (SCLY, EC 4.4.1.16); H2S and H2Se donors and selenium and sulfane sulfur-containing compounds, as well as inhibitors of H2S and H2Se production.

Research articles, reviews, and communications are welcome. For authors interested in submitting a paper, please refer to Biomolecules “Author Guidelines”.

Prof. Dr. Maria Wrobel
Dr. Halina Jurkowska
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. Biomolecules is an international peer-reviewed open access monthly 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

  • cysteine
  • selenocysteine
  • taurine
  • hydrogen sulfide
  • hydrogen selenide
  • selenoproteins
  • sulfurtransferases
  • H2S precursors
  • antioxidants
  • diseases related to sulfur metabolism

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Published Papers (3 papers)

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Research

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17 pages, 1522 KB  
Article
Oxidative Stress and Iron Addiction: A Comparative Study of 1321N1 Astrocytoma and T98G Glioblastoma Cells with Differential Expression of L-Cysteine-Metabolizing Enzymes
by Halina Jurkowska, Ewa Jasek-Gajda, Konrad Kaleta, Leszek Rydz, Dominika Szlęzak and Maria Wróbel
Biomolecules 2025, 15(10), 1478; https://doi.org/10.3390/biom15101478 - 20 Oct 2025
Abstract
Gliomas are central nervous system primary tumors that are distinguished by heterogeneity, broad-based infiltration, and metabolic reprogramming that sustains proliferation, invasion, and therapy refractoriness. Oxidative stress—a state of imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense—and disturbed iron [...] Read more.
Gliomas are central nervous system primary tumors that are distinguished by heterogeneity, broad-based infiltration, and metabolic reprogramming that sustains proliferation, invasion, and therapy refractoriness. Oxidative stress—a state of imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense—and disturbed iron metabolism are central drivers of glioma biology. The aim of this study was to evaluate ROS production, sulfane sulfur levels, the expression of proteins with antioxidant properties, such as L-cysteine-metabolizing enzymes (cystathionine β-synthase, CBS; cysteine dioxygenase 1, CDO1; cystathionine γ-lyase, CTH; 3-mercaptopyruvate sulfurtransferase, MPST; thiosulfate sulfurtransferase, TST) and non-enzymatic proteins (p53; transferrin receptor 1, TfR1), in human brain cancer cells differing in malignancy: 1321N1 astrocytoma and T98G glioblastoma. Western blotting analysis demonstrated that the expression of CBS, CDO1, and TfR1 was significantly increased in T98G cells, while CTH, MPST, TST, and p53 were comparably expressed in both cell lines. Quantitative assays revealed that T98G cells harbored significantly higher sulfane sulfur levels and higher numbers of ROS-positive cells compared to 1321N1 cells. Our results suggest that glioblastoma but not astrocytoma cells adapt sulfur and iron metabolism to provide proliferation capacity against chronic oxidative stress. It seems that CBS as well as CDO1 may significantly increase the antioxidant potential of T98G cells. In summary, this study suggests a differing metabolic vulnerability identifiable only in high-grade glioma cells and provides a potential novel molecular target for therapy. Full article
(This article belongs to the Special Issue Cysteine and Selenocysteine in Antioxidant Defense, Protein Synthesis and Signaling Pathways)
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Review

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33 pages, 1724 KB  
Review
Retinal Gatekeepers: Molecular Mechanism and Therapeutic Role of Cysteine and Selenocysteine
by Eleonora Maceroni, Annamaria Cimini, Massimiliano Quintiliani, Michele d’Angelo and Vanessa Castelli
Biomolecules 2025, 15(8), 1203; https://doi.org/10.3390/biom15081203 - 21 Aug 2025
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Abstract
Oxidative stress is a key contributor to retinal degeneration, as the retina is highly metabolically active and exposed to constant light stimulation. This review explores the crucial roles of cysteine and selenocysteine in redox homeostasis and retinal protection. Cysteine, primarily synthesized via the [...] Read more.
Oxidative stress is a key contributor to retinal degeneration, as the retina is highly metabolically active and exposed to constant light stimulation. This review explores the crucial roles of cysteine and selenocysteine in redox homeostasis and retinal protection. Cysteine, primarily synthesized via the transsulfuration pathway, is the rate-limiting precursor for glutathione (GSH), the most abundant intracellular antioxidant. Selenocysteine enables the enzymatic activity of selenoproteins, particularly glutathione peroxidases (GPXs), which counteract reactive oxygen species (ROS). Experimental evidence from retinal models confirms that depletion of cysteine or selenocysteine results in impaired antioxidant defense and photoreceptor death. Furthermore, dysregulation of these amino acids contributes to the pathogenesis of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Therapeutic approaches including N-acetylcysteine, selenium compounds, and gene therapy targeting thioredoxin systems have demonstrated protective effects in preclinical studies. Targeting cysteine and selenocysteine-dependent systems, as well as modulating the KEAP1–NRF2 pathway, may offer promising strategies for managing retinal neurodegeneration. Advancing our understanding of redox mechanisms and their role in retinal cell viability could unlock new precision treatment strategies for retinal diseases. Full article
(This article belongs to the Special Issue Cysteine and Selenocysteine in Antioxidant Defense, Protein Synthesis and Signaling Pathways)
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33 pages, 938 KB  
Review
Exploring the Antioxidant Roles of Cysteine and Selenocysteine in Cellular Aging and Redox Regulation
by Marta Pace, Chiara Giorgi, Giorgia Lombardozzi, Annamaria Cimini, Vanessa Castelli and Michele d’Angelo
Biomolecules 2025, 15(8), 1115; https://doi.org/10.3390/biom15081115 - 3 Aug 2025
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Abstract
Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, [...] Read more.
Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, first proposed by Denham Harman in 1956, highlights the role of reactive oxygen species (ROS), byproducts of normal metabolism, in driving oxidative stress and age-related degeneration. Emerging evidence emphasizes the importance of redox imbalance in the onset of neurodegenerative diseases and aging. Among the critical cellular defenses against oxidative stress are sulfur-containing amino acids, namely cysteine (Cys) and selenocysteine (Sec). Cysteine serves as a precursor for glutathione (GSH), a central intracellular antioxidant, while selenocysteine is incorporated into key antioxidant enzymes such as glutathione peroxidases (GPx) and thioredoxin reductases (TrxR). These molecules play pivotal roles in neutralizing ROS and maintaining redox homeostasis. This review aims to provide an updated and critical overview of the role of thiol-containing amino acids, specifically cysteine and selenocysteine, in the regulation of redox homeostasis during aging. Full article
(This article belongs to the Special Issue Cysteine and Selenocysteine in Antioxidant Defense, Protein Synthesis and Signaling Pathways)
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