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  • Open Access

    REVIEW

    Melatonin and Mitochondrial Function: Insights into Bioenergetics, Dynamics, and Gene Regulation

    Silvia Carloni1,*, Maria Gemma Nasoni1, Serafina Perrone2, Erik Bargagni1, Carla Gentile3, Walter Manucha4, Russel J. Reiter5, Francesca Luchetti1,*, Walter Balduini1,*

    BIOCELL, Vol.50, No.2, pp. 1-22, 2026, DOI:10.32604/biocell.2025.073776 - 14 February 2026

    Abstract Mitochondria are central regulators of cellular energy metabolism, redox balance, and survival, and their dysfunction contributes to neurodegenerative, cardiovascular, and metabolic diseases, as well as aging. Beyond its role as a circadian hormone, melatonin is now recognized as a key modulator of mitochondrial physiology. This review provides an overview of the mechanisms by which melatonin can preserve mitochondrial function through multifaceted mechanisms. Experimental evidence shows that melatonin enhances the activity of electron transport chain (ETC) complexes, stabilizes the mitochondrial membrane potential (Δψ), and prevents cardiolipin (CL) peroxidation, thereby limiting permeability transition pore (mPTP) opening and… More >

  • Open Access

    REVIEW

    Natural Killer Cell Cytotoxicity: STAT3 Interactions with NF-κB Dimer Composition Modulate Mitochondrial Melatonergic Pathway: Tumor, and Viral Infection Treatment Implications#

    George Anderson*

    BIOCELL, Vol.50, No.2, 2026, DOI:10.32604/biocell.2025.073221 - 14 February 2026

    Abstract As natural killer (NK) cells eliminate cancer cells and virus-infected cells, as well as modulate various other medical conditions, including aging-associated conditions such as neurodegenerative disorders, understanding NK cell regulation is of considerable clinical importance. This article reviews the role of circadian processes (melatonin and the cortisol system), aryl hydrocarbon receptor, and vagal nerve in the modulation of NK cell function, highlighting the importance of the endogenous mitochondrial melatonergic pathway in NK cells. As circadian and exogenous melatonin increase NK cell cytotoxicity, the presence of the endogenous melatonergic pathway may be of some importance not… More >

  • Open Access

    REVIEW

    Melatonin as a Neuroprotective Agent in Ischemic Stroke: Mechanistic Insights Centralizing Mitochondria as a Potential Therapeutic Target

    Mayuri Shukla1, Soraya Boonmag2, Parichart Boontem1, Piyarat Govitrapong1,*

    BIOCELL, Vol.50, No.1, 2026, DOI:10.32604/biocell.2025.072557 - 23 January 2026

    Abstract Ischemic stroke is one of the major causes of long-term disability and mortality worldwide. It results from an interruption in the cerebral blood flow, triggering a cascade of detrimental events like oxidative stress, mitochondrial dysfunction, neuroinflammation, excitotoxicity, and apoptosis, causing neuronal injury and cellular death. Melatonin, a pleiotropic indoleamine produced by the pineal gland, has multifaceted neuroprotective effects on stroke pathophysiology. Interestingly, the serum melatonin levels are associated with peroxidation and antioxidant status, along with mortality score in patients with severe middle cerebral artery infarction. Melatonin exhibits strong antioxidant, anti-inflammatory, and anti-apoptotic properties and preserves More >

  • Open Access

    ARTICLE

    Melatonin and Related Compounds as Enzymatic Antioxidants: A Comprehensive Theoretical Study

    Luis Felipe HernáNdez-Ayala1, Russel J. Reiter2, Annia Galano1,*

    BIOCELL, Vol.50, No.1, 2026, DOI:10.32604/biocell.2025.071635 - 23 January 2026

    Abstract Objectives: Oxidative stress (OS) plays a pivotal role in chronic and neurodegenerative diseases, which has sparked interest in molecules that modulate redox-regulating enzymes. Melatonin and its metabolites exhibit antioxidant properties; however, their molecular mechanisms of enzymatic and transcriptional modulation remain unclear. This study aimed to investigate, through an exploratory in silico approach, the interactions of melatonin and related compounds with OS-related enzymes to generate hypotheses about their role in cellular redox control. Methods: A rational selection of antioxidant, pro-oxidant, and transcriptional targets was performed. Ligands were optimized at the DFT level (M05-2X/6-311+G(d,p)) and docked to OS… More >

  • Open Access

    REVIEW

    The Warburg Effect Beyond Cancer: Melatonin as a Metabolic Modulator in Non-Neoplastic Disorders

    JOSé A. BOGA1,2, ANA COTO-MONTES2,3,*, RUSSEL J. REITER4

    BIOCELL, Vol.50, No.1, 2026, DOI:10.32604/biocell.2025.068245 - 23 January 2026

    Abstract Aerobic glycolysis, also known as the Warburg effect, and the accumulation of lactate that it causes, are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders. This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverse Warburg-effect-like metabolic reprogramming. Literature on neurodegeneration, age-related sarcopenia, type 2 diabetes, chronic kidney disease, heart failure and pulmonary arterial hypertension (PAH) has been reviewed and synthesised. In all of these conditions, hypoxia-inducible factor 1α (HIF-1α) and pyruvate dehydrogenase kinase 4 (PDK4) inhibit the pyruvate dehydrogenase complex. This diverts pyruvate away… More >

  • Open Access

    ARTICLE

    Melatonin Priming Enhances Potassium Dichromate Stress Tolerance and Morpho-Physiological Performance via Genetic Modulation in Melon (Cucumis melo L.) Plant

    Tai Liu1,#, Huichun Xu1,#, Sikandar Amanullah2,*, Ye Che1, Ling Zhang1, Zeyu Jiang1, Weiyi Bi1, Lei Zhu1, Di Wang1,*

    Phyton-International Journal of Experimental Botany, Vol.94, No.12, pp. 4117-4137, 2025, DOI:10.32604/phyton.2025.074131 - 29 December 2025

    Abstract Heavy metal accumulation in agricultural soil is primarily driven by pesticides, polluted water, and industrial gas emissions, which pose threats to sustainable crop production. Chromium (Cr) stress has an adverse impact on plant development and metabolism, but approaches to reduce its toxicity and enhance plant resistance remain limited. Melatonin is a potent antioxidant involved in regulating various morpho-physiological functions of plants under different abiotic stresses. In this study, we investigated the impact of exogenous melatonin to mitigate the negative effects of potassium dichromate (PD) stress in melon plants and analyzed genetic modulation of morphological, physiological,… More >

  • Open Access

    ARTICLE

    Synergistic Effects of Melatonin and Methyl Jasmonate in Mitigating Drought-Induced Oxidative Stress in Common Bean (Phaseolus vulgaris)

    Totan Kumar Ghosh1, Md. Roushonuzzaman Rakib1, Munna1, S. M. Zubair AL-Meraj1, Md. Moshiul Islam2, Anika Nazran1, Mohammad Golam Mostofa3,*

    Phyton-International Journal of Experimental Botany, Vol.94, No.12, pp. 3925-3943, 2025, DOI:10.32604/phyton.2025.073382 - 29 December 2025

    Abstract The productivity of common bean (Phaseolus vulgaris L.), an economically important legume, is severely hindered by drought stress. While melatonin (Mel) and methyl jasmonate (MeJA) are known to alleviate abiotic stresses, their combined effects in mitigating drought-induced oxidative stress are unknown. Here, we examined the synergistic effects of Mel and MeJA in alleviating drought-associated oxidative damage in common bean. Compared with well-watered controls, drought stress caused a significant decline in plant biomass, photosynthetic pigments, and photosystem II efficiency (Fv/Fm). Drought also significantly increased hydrogen peroxide (H2O2) accumulation, which likely contributed to membrane lipid peroxidation, as indicated by… More >

  • Open Access

    REVIEW

    Mitochondrial Stress, Melatonin, and Neurodegenerative Diseases: New Nanopharmacological Approaches

    Virna Margarita Martín Giménez1, SebastiáN GarcíA MenéNdez2,3, Luiz Gustavo A. Chuffa4, Vinicius Augusto SimãO4, Russel J. Reiter5, Ramaswamy Sharma6, Walter Balduini7, Carla Gentile8, Walter Manucha2,3,*

    BIOCELL, Vol.49, No.12, pp. 2245-2282, 2025, DOI:10.32604/biocell.2025.071830 - 24 December 2025

    Abstract Neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss, which is closely linked to mitochondrial dysfunction. These pathologies involve a complex interplay of genetics, protein misfolding, and cellular stress, culminating in impaired energy metabolism, an increase in reactive oxygen species (ROS), and defective mitochondrial quality control. The accumulation of damaged mitochondria and dysregulation of pathways such as the Integrated Stress Response (ISR) are central to the pathogenesis of these conditions. This review explores the critical relationship between mitochondrial stress… More >

  • Open Access

    ARTICLE

    Melatonin Enhances Antioxidant Defense and Physiological Stability in Grapevine (Vitis vinifera L.) Cultivars ‘Merlot’ and ‘Erciş’ under UV-B Stress

    Sena Yıldız1, Nurhan Keskin2,*, Birhan Kunter3, Harlene Hatterman-Valenti4, Ozkan Kaya4,5,*

    Phyton-International Journal of Experimental Botany, Vol.94, No.11, pp. 3471-3492, 2025, DOI:10.32604/phyton.2025.073180 - 01 December 2025

    Abstract Climate change-driven environmental stresses, particularly ultraviolet-B (UV-B) radiation, pose severe threats to grapevine (Vitis vinifera L.) productivity and physiological stability. This study investigated the protective role of melatonin in in vitro plantlets of two grapevine cultivars, ‘Merlot’ and ‘Erciş’, subjected to low (≈8.25 μW cm−2, 16 h) and high (≈33 μW cm−2, 4 h) UV-B exposure. Significant cultivar-specific responses were observed (p < 0.001). The ‘Erciş’ cultivar exhibited higher oxidative stress, with malondialdehyde (MDA) levels reaching 24.30 mmol g−1 FW in control plants compared with 14.91 ± 0.25 mmol g−1 FW in ‘Merlot’. Melatonin provided dose-dependent mitigation, reducing MDA to… More >

  • Open Access

    REVIEW

    Mechanistic Insights into the Role of Melatonin in Cancer Cell Chemoresistance

    Russel J. Reiter1,*, Ramaswamy Sharma2,*, Walter Manucha3, Walter Balduini4, Doris Loh5, Demetrios A. Spandidos6, Alejandro Romero7, Vasiliki E. Georgakopoulou8, Wei Zhu9

    BIOCELL, Vol.49, No.11, pp. 2033-2067, 2025, DOI:10.32604/biocell.2025.067661 - 24 November 2025

    Abstract The development of cancer cell resistance to conventional treatments continues to be a major obstacle in the successful treatment of tumors of many types. The discovery of a highly efficient direct and indirect free radical scavenger, melatonin, in the mitochondrial matrix may be a factor in determining both the occurrence of cancer cell drug insensitivity as well as radioresistance. This relates to two of the known hallmarks of cancer, i.e., exaggerated free radical generation in the mitochondria and the development of Warburg type metabolism (glycolysis). The hypothesis elaborated in this report assumes that the high… More >

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