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ROS Signalling and Cell Turnover

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 3570

Special Issue Editor


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Guest Editor
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy
Interests: metabolism; lipid droplets; nanoparticles; ROS; cancer therapy; redox homeostasis; leukemia; mitochondria; oncogenic virus; apoptosis

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS) are a group of chemically reactive molecules that are crucial in controlling metabolic pathways. Several normal biochemical processes lead to the formation of ROS, which are counteracted by antioxidant systems that keep ROS levels low.

Importantly, ROS are essential second messengers that regulate multiple signal transduction pathways and, in this way, control cell fate. 

ROS exert their function by modifying the redox state of cysteine residues in transducing proteins, including protein kinases and transcription factors. Thus, critical decisions on cell fate, such as cell division, survival, or activation of cell death programs, depend on ROS levels, which result from a delicate balance between ROS-producing and ROS-scavenging pathways.

ROS also plays a fundamental role in inflammation, immune response, cancer, and cardiovascular and neurodegenerative diseases.

This Special Issue will focus on redox homeostasis in physiology and diseases. Original manuscripts and reviews covering these topics are welcome.

Dr. Micol Silic-Benussi
Guest Editor

Manuscript Submission Information

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Keywords

  • metabolism
  • lipid droplets
  • nanoparticles
  • ROS
  • cancer therapy
  • redox homeostasis
  • mitochondria
  • cell death

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Published Papers (2 papers)

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Research

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21 pages, 2678 KB  
Article
Potassium-Hydroxide-Based Extraction of Nicotinamide Adenine Dinucleotides from Biological Samples Offers Accurate Assessment of Intracellular Redox Status
by Tamas Faludi, Daniel Krakko, Jessica Nolan, Robert Hanczko, Akshay Patel, Zach Oaks, Evan Ruggiero, Joshua Lewis, Xiaojing Wang, Ting-Ting Huang, Ibolya Molnar-Perl and Andras Perl
Int. J. Mol. Sci. 2025, 26(21), 10371; https://doi.org/10.3390/ijms262110371 - 24 Oct 2025
Viewed by 761
Abstract
The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is a primary electron donor for both antioxidant enzymes, such as glutathione reductase, and pro-oxidant enzymes, such as NADPH oxidases that produce reactive oxygen species (ROS) and nitric oxide synthases that generate nitric oxide [...] Read more.
The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is a primary electron donor for both antioxidant enzymes, such as glutathione reductase, and pro-oxidant enzymes, such as NADPH oxidases that produce reactive oxygen species (ROS) and nitric oxide synthases that generate nitric oxide which act as signaling molecules. Monitoring NADPH levels, NADPH/NADP+ ratio, and especially distinguishing from NADH, provides vital information about cellular redox status, energy generation, survival, lineage specification, and death pathway selection. NADPH detection is key to understanding metabolic reprogramming in cancer, aging, and cardiovascular, hormonal, neurodegenerative, and autoimmune diseases. Liquid chromatography combined with mass spectrometry (LC-MS) is crucial for NADPH detection in redox signaling because it offers the high sensitivity, specificity, and comprehensive profiling needed to quantify this vital but labile redox cofactor in complex biological samples. Using hepatoma cell lines, liver tissues, and primary hepatocytes from mice lacking transaldolase or nicotinamide nucleotide transhydrogenase, or having lupus, this study demonstrates that accurate measurement of NADPH depends on its preservation in reduced form which can be optimally achieved by extraction of metabolites in alkaline solution, such as 0.1 M potassium hydroxide (KOH) in comparison to 80% methanol (MeOH) alone or 40:40:20 methanol/acetonitrile/formic acid solution. While KOH extraction coupled with hydrophilic interaction liquid chromatography (HILIC) and mass spectrometry most reliably detects NADPH, NADP, NADH, NAD, polyamines, and polyols, MeOH extraction is best suited for detection of glutathione and overall discrimination between complex metabolite extracts. This study therefore supports performing parallel KOH and MeOH extractions to enable comprehensive metabolomic analysis of redox signaling. Full article
(This article belongs to the Special Issue ROS Signalling and Cell Turnover)
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Review

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49 pages, 8236 KB  
Review
Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond
by Noah Sendtner, Rebecca Seitz, Noah Brandl, Martina Müller and Karsten Gülow
Int. J. Mol. Sci. 2025, 26(20), 10240; https://doi.org/10.3390/ijms262010240 - 21 Oct 2025
Cited by 2 | Viewed by 2206
Abstract
Reactive oxygen species (ROS) are versatile determinants of cell fate, tipping the balance between survival and death. By exceeding critical thresholds or perturbing compartment-specific signaling, ROS can initiate, modulate, or suppress regulated cell death (RCD). Importantly, their influence extends across the full spectrum [...] Read more.
Reactive oxygen species (ROS) are versatile determinants of cell fate, tipping the balance between survival and death. By exceeding critical thresholds or perturbing compartment-specific signaling, ROS can initiate, modulate, or suppress regulated cell death (RCD). Importantly, their influence extends across the full spectrum of currently characterized RCD modalities. 19 distinct forms of cell death—including both long-established and recently described entities—are shaped by ROS, either as triggers, modulators, or inhibitors. Beyond pathway-specific effects, ROS promote crosstalk between death programs, enabling switches from one mode to another and determining whether outcomes are inflammatory or non-inflammatory. By systematically integrating 19 RCD types, the unifying role of ROS emerges as both gatekeeper and connector of diverse death pathways. Such a comprehensive perspective underscores the centrality of redox imbalance in cell fate control and highlights its broader implications for inflammation and disease. Full article
(This article belongs to the Special Issue ROS Signalling and Cell Turnover)
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