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Melatonin and Mitochondria: Exploring New Frontiers

Submission Deadline: 01 September 2025 (closed) View: 7384 Submit to Journal

Guest Editor(s)

Russel J. Reiter (Honorary Guest Editor)

Email: reiter@uthscsa.edu

Affiliation: Department of Cellular & Structural Biology, The UT Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA

Homepage:

Research Interests: melatonin, free radicals of disease processes and aging, oxygen derivatives, neurodegenerative diseases


Doris Loh (Managing Guest Editor)

Email: lohdoris23@gmail.com

Affiliation: Independent Researcher, Marble Falls, TX, USA

Homepage:

Research Interests: melatonin, ascorbic acid, aging, mitochondria, biomolecular condensates


Summary

Melatonin, an ancient and evolutionarily successful indoleamine, first appeared in Archaea and Bacteria approximately 4 billion years ago. It has since been identified as a ubiquitous molecule in the mitochondria and chloroplasts of tested Eukarya species, regardless of the presence of a pineal gland. Current scientific consensus suggests that mitochondrial melatonin accounts for over 95% of total organismal melatonin production, highlighting the diverse pleiotropic effects of this compound in various biological systems.

 

In plants and unicellular organisms, melatonin production is highly responsive to both endogenous and exogenous stress, suggesting its role as a protective agent. However, the relationship between mitochondrial melatonin production and pineal melatonin synthesis under cellular stress remains poorly understood. Of particular importance is the realization that many experimental models, including inbred rodents and transgenic animals, exhibit reduced circulating melatonin due to truncated AANAT (SNAT) genes in their mitochondria, potentially complicating the interpretation of findings in fields such as oncology, neurobiology, and other areas of health and disease research.

 

This special issue aims to delve into the intriguing roles of mitochondrial melatonin beyond the pineal gland, with a focus on how it may interact with pineal melatonin in maintaining cellular homeostasis and mitigating disease. We seek to explore how mitochondrial melatonin influences various biological processes and how these innovative insights might open up new therapeutic avenues for treating conditions such as neurodegenerative diseases, metabolic disorders, and cancer.

 

Key areas of focus include, but are not limited to:

1. Oxidative Phosphorylation and ATP Synthesis:

   - Investigating how mitochondrial melatonin regulates oxidative phosphorylation and energy production.

2. Mitochondrial Bioenergetics, Dynamics, Morphology, and Proteostasis:

   - Exploring the role of melatonin in maintaining mitochondrial structure and function, including the regulation of mitochondrial fission, fusion, autophagy, and cristae architecture.

3. Mitochondrial Transcription and Translation:

   - Understanding how melatonin influences mitochondrial gene expression and protein synthesis, particularly in response to cellular stress or damage.

 

By compiling cutting-edge research on these topics, this special issue will provide a deeper understanding of the functions of mitochondrial melatonin and its potential applications in health and disease. We invite original research articles, reviews, and perspectives that advance knowledge on this topic and contribute to shaping future research directions in the field.


Keywords

melatonin, mitochondria, oxidative phosphorylation, bioenergetics, mitochondrial dynamics, proteostasis, transcription, translation, neurodegenerative diseases, metabolic syndromes, cancer, cellular stress

Published Papers


  • Open Access

    REVIEW

    Mitochondria as the Bridge between Injury and Protection: The Role of Melatonin in Non-Steroidal Anti-Inflammatory Drug-Induced Gastric Ulcers

    Debasish Bandyopadhyay, Romit Majumder, Madhuri Datta, Adrita Banerjee, Aindrila Chattopadhyay
    BIOCELL, Vol.50, No.6, 2026, DOI:10.32604/biocell.2026.075963
    (This article belongs to the Special Issue: Melatonin and Mitochondria: Exploring New Frontiers)
    Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed, but their long-term use frequently results in gastric mucosal injury. Emerging evidence indicates that, beyond cyclooxygenase inhibition, mitochondrial dysfunction represents a central mechanism driving NSAID-induced gastric epithelial damage. This review aims to critically synthesize current evidence on mitochondria-centered pathways involved in NSAID-induced gastric ulceration and to evaluate the therapeutic relevance of melatonin in this context. We highlight how NSAIDs impair mitochondrial bioenergetics, promote excessive reactive oxygen species generation, disrupt membrane potential, and activate apoptotic signaling, thereby compromising mucosal integrity. Importantly, melatonin exerts multifaceted gastroprotective actions by preserving mitochondrial 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
    (This article belongs to the Special Issue: Melatonin and Mitochondria: Exploring New Frontiers)
    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 Shukla, Soraya Boonmag, Parichart Boontem, Piyarat Govitrapong
    BIOCELL, Vol.50, No.1, 2026, DOI:10.32604/biocell.2025.072557
    (This article belongs to the Special Issue: Melatonin and Mitochondria: Exploring New Frontiers)
    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 >

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