Role of Mitochondria and ROS in Health and Disease

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "ROS, RNS and RSS".

Deadline for manuscript submissions: 25 June 2025 | Viewed by 8796

Special Issue Editors


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Guest Editor Assistant
Department of Biology, University Federico II of Naples, Via Cinthia 26, 80126 Naples, Italy
Interests: oxidative stress; hyperthyroidism; mitochondria; vitamin E; ROS; antioxidant; insulin resistance

Special Issue Information

Dear Colleagues,

Mitochondria are complex organelles that perform multiple functions in eukaryotic cells and interact and communicate with all cellular organelles, including endoplasmic reticulum, lysosomes, cytoskeleton, peroxisomes, and the nucleus. Their principal role is to serve as a primary site for energy production in a process accompanied by the formation of potentially harmful substances, such as radicals and other reactive oxygen species (ROS), which can damage, among others, the same mitochondria that produce them. Mitochondria possess an efficient antioxidant system to counteract the harmful effects of ROS, which also makes them capable of eliminating ROS produced by other cellular sources, acting as a hub for regulating cellular ROS content.

Under basal conditions, a low ROS production is critical since ROS function as messenger molecules in various physiological processes, including adaptation to hypoxia, the regulation of autophagy, immunity, differentiation, longevity, and adaptation to exercise. Indeed, ROS are necessary to improve mitochondrial health and activate their proliferation during physical activity.

In some circumstances, including mitochondrial DNA mutations, infections, ageing, and a lack of physical activity, ROS production can increase, thus activating a vicious cycle that leads to mitochondrial dysfunction. Indeed, when mitochondrial ROS production increases, damage to components of the respiratory chain and enzymes of the Krebs cycle occurs, inducing a positive feedback loop that intensifies ROS production, resulting in damage to various cellular structures. The accumulation of oxidative damage to cellular structures and the impairment of mitochondrial wellbeing both contribute to the development of many non-communicable diseases, including age-related macular disease (AMD), neurological disorders, and metabolic diseases. This observation highlights the urgent need for a comprehensive understanding of the pathways involving ROS, with a particular focus on identifying key targets for effective therapeutic interventions.

Dr. Paola Venditti
Dr. Gaetana Napolitano
Dr. Gianluca Fasciolo
Guest Editors

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Keywords

  • ROS
  • mitochondria
  • antioxidant
  • oxidative stress
  • neurological diseases
  • metabolic diseases
  • retinal diseases
  • mitochondrial disfunctions
  • mitochondria endoplasmic reticulum communication
  • mitochondrial bioenergetics
  • ageing
  • physical activity

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Published Papers (6 papers)

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Research

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27 pages, 4782 KiB  
Article
Large Fibrous Connective Tissue Reduces Oxidative Stress to Form a Living Cell Scaffold in Adipose Grafts
by Qiang Yue, Zilong Cao, Tiran Zhang, Ningbei Yin and Liqiang Liu
Antioxidants 2025, 14(3), 270; https://doi.org/10.3390/antiox14030270 - 26 Feb 2025
Viewed by 458
Abstract
This study aimed to investigate the mechanisms by which large fibrous connective (LFC) tissue enhances fat graft survival in fat transplantation. A block fat graft model demonstrated that intact fat containing LFC showed significantly higher survival rates compared with liposuctioned fat. In the [...] Read more.
This study aimed to investigate the mechanisms by which large fibrous connective (LFC) tissue enhances fat graft survival in fat transplantation. A block fat graft model demonstrated that intact fat containing LFC showed significantly higher survival rates compared with liposuctioned fat. In the center of intact grafts, viable fat cells surrounded the LFC, forming a mesh-like living tissue structure. Proteomics of the extracellular matrix (ECM) adjacent to LFC (ALFC) and distant to LFC (DLFC) revealed significant differences in mitochondrial aspects. Staining of LFC tissue showed that it contains a large number of blood vessels and mitochondria, and exhibits stronger antioxidant capacity (p < 0.05) compared with adipose tissue. By mixing LFC with liposuctioned fat and transplanting into nude mice, histological sections showed that LFC promotes SOD1 expression, enhances respiratory chain RNA expression, and reduces ROS and inflammation. Pure mitochondrial-assisted fat transplantation only reduced short-term graft inflammation without improving long-term survival rates. In conclusion, LFC enhances long-term survival rates by reducing oxidative stress in fat grafts and forming a center for fat cell survival, thereby overcoming distance limitations. This represents a novel mechanism distinct from classical fat survival models and provides a reference for clinical practice. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease)
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23 pages, 4548 KiB  
Article
ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone-Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts
by Aya Darawsha, Aviram Trachtenberg and Yoav Sharoni
Antioxidants 2024, 13(8), 1019; https://doi.org/10.3390/antiox13081019 - 21 Aug 2024
Cited by 2 | Viewed by 1641
Abstract
Skin aging is associated with the increased production of mitochondrial reactive oxygen species (mtROS) due to mitochondrial dysfunction, and various phytonutrients and estrogens have been shown to improve skin health. Thus, the aim of the current study was to examine damage to dermal [...] Read more.
Skin aging is associated with the increased production of mitochondrial reactive oxygen species (mtROS) due to mitochondrial dysfunction, and various phytonutrients and estrogens have been shown to improve skin health. Thus, the aim of the current study was to examine damage to dermal fibroblasts by chemically induced mitochondrial dysfunction and to study the mechanism of the protective effects of carotenoids, polyphenols, and estradiol. Rotenone, a Complex I inhibitor, caused mitochondrial dysfunction in human dermal fibroblasts, substantially reducing respiration and ATP levels, followed by increased mitochondrial and cytosolic ROS, which resulted in apoptotic cell death, an increased number of senescent cells, increased matrix metalloproteinase-1 (MMP1) secretion, and decreased collagen secretion. Pre-treatment with carotenoid-rich tomato extracts, rosemary extract, and estradiol reversed these effects. These protective effects can be partially explained by a cooperative activation of antioxidant response element (ARE/Nrf2) transcriptional activity by the protective compounds and rotenone, which led to the upregulation of antioxidant proteins such as NQO1. To determine if ARE/Nrf2 activity is crucial for cell protection, we inhibited it using the Nrf2 inhibitors ML385 and ochratoxin A. This inhibition markedly reduced the protective effects of the test compounds by diminishing their effect to reduce cytosolic ROS. Our study results indicate that phytonutrients and estradiol protect skin cells from damage caused by mtROS, and thus may delay skin cell senescence and improve skin health. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease)
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18 pages, 11060 KiB  
Article
Sodium Selenite Induces Autophagy and Apoptosis in Cervical Cancer Cells via Mitochondrial ROS-Activated AMPK/mTOR/FOXO3a Pathway
by Cunqi Lv, Qingyu Zeng, Lei Qi, Yuanyuan Wang, Jiacheng Li, Huixin Sun, Linlin Du, Shuxiu Hao, Guijin Li, Chen Feng, Yu Zhang, Cheng Wang, Xinshu Wang, Rong Ma, Tong Wang and Qi Li
Antioxidants 2024, 13(8), 1004; https://doi.org/10.3390/antiox13081004 - 19 Aug 2024
Cited by 6 | Viewed by 2211
Abstract
Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been [...] Read more.
Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS’s anti-CC effects, and SS’s inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease)
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Review

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25 pages, 1661 KiB  
Review
Mitochondrial Dysfunction in Endothelial Cells: A Key Driver of Organ Disorders and Aging
by Elena Grossini, Sakthipriyan Venkatesan and Mohammad Mostafa Ola Pour
Antioxidants 2025, 14(4), 372; https://doi.org/10.3390/antiox14040372 - 21 Mar 2025
Cited by 1 | Viewed by 1192
Abstract
Mitochondria are of great importance in cell biology since they are major sites of adenosine triphosphate (ATP) production and are widely involved in different cellular pathways involved in the response to stress. During ATP production, reactive oxygen species (ROS) can be produced. While [...] Read more.
Mitochondria are of great importance in cell biology since they are major sites of adenosine triphosphate (ATP) production and are widely involved in different cellular pathways involved in the response to stress. During ATP production, reactive oxygen species (ROS) can be produced. While a small amount of ROS may be important for the regulation of physiological processes, at elevated levels they can turn into harmful agents leading to cellular damage. From a pathological perspective, it could be particularly interesting to focus on mitochondrial function in endothelial cells since they may be involved in the development of aging and in the onset of different diseases, including renal, cardio-metabolic, liver and neurodegenerative ones. However, to date, there are no surveys which address the above issues. To fill this gap, it may be valuable to collect recent findings about the role of mitochondria in the regulation of endothelial function, not only to increase knowledge about it but also for clinical applications. Here, we overview the most recent knowledge about the above issues in the view of characterizing the role of mitochondria in endothelial cells as an innovative potential target for the prevention of aging, as well as the treatment of the above pathological conditions. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease)
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24 pages, 1821 KiB  
Review
Unraveling Mitochondrial Reactive Oxygen Species Involvement in Psoriasis: The Promise of Antioxidant Therapies
by Hajar Ahmad Jamil and Norwahidah Abdul Karim
Antioxidants 2024, 13(10), 1222; https://doi.org/10.3390/antiox13101222 - 11 Oct 2024
Viewed by 2186
Abstract
Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and aberrant keratinocyte proliferation. Despite tremendous advances in understanding its etiology, effective therapies that target its fundamental mechanisms remain necessary. Recent research highlights the role of reactive oxygen species dysregulation and mitochondrial [...] Read more.
Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and aberrant keratinocyte proliferation. Despite tremendous advances in understanding its etiology, effective therapies that target its fundamental mechanisms remain necessary. Recent research highlights the role of reactive oxygen species dysregulation and mitochondrial dysfunction in psoriasis pathogenesis. Mitochondrial reactive oxygen species mediate cellular signaling pathways involved in psoriasis, such as proliferation, apoptosis, and inflammation, leading to oxidative stress, exacerbating inflammation and tissue damage if dysregulated. This review explores oxidative stress biomarkers and parameters in psoriasis, including myeloperoxidase, paraoxonase, sirtuins, superoxide dismutase, catalase, malondialdehyde, oxidative stress index, total oxidant status, and total antioxidant status. These markers provide insights into disease mechanisms and potential diagnostic and therapeutic targets. Modulating mitochondrial reactive oxygen species levels and enhancing antioxidant defenses can alleviate inflammation and oxidative damage, improving patient outcomes. Natural antioxidants like quercetin, curcumin, gingerol, resveratrol, and other antioxidants show promise as complementary treatments targeting oxidative stress and mitochondrial dysfunction. This review aims to guide the development of personalized therapeutic methods and diagnostic techniques, emphasizing the importance of comprehensive clinical studies to validate the efficacy and safety of these interventions, paving the way for more effective and holistic psoriasis care. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease)
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Other

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6 pages, 517 KiB  
Opinion
ROMO1: A Distinct Mitochondrial Protein with Dual Roles in Dynamics and Function
by Angel Yordanov and Eva Tsoneva
Antioxidants 2025, 14(5), 540; https://doi.org/10.3390/antiox14050540 - 30 Apr 2025
Viewed by 87
Abstract
Reactive oxygen species modulator 1 (ROMO1) is a nuclear-encoded inner mitochondrial protein known for its dual role as a modulator of reactive oxygen species (ROS) and a non-selective ion channel. Initially identified for its role in ROS production, ROMO1 has garnered attention for [...] Read more.
Reactive oxygen species modulator 1 (ROMO1) is a nuclear-encoded inner mitochondrial protein known for its dual role as a modulator of reactive oxygen species (ROS) and a non-selective ion channel. Initially identified for its role in ROS production, ROMO1 has garnered attention for its functional properties as a non-selective ion channel that regulates ion homeostasis in mitochondria. This article examines ROMO1 from both perspectives, emphasizing its structural and functional characteristics, physiological roles, and implications in health and disease. Understanding ROMO1’s dual functionality provides insight into its potential as a therapeutic target for oxidative stress-related disorders, especially cancer progression. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease)
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