Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics
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Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s). Melatonin protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting the mitochondrial permeability transition pore (MPTP), and activating uncoupling proteins (UCPs). Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions. In addition, mitochondrial biogenesis and dynamics is also regulated by melatonin. In most cases, melatonin reduces mitochondrial fission and elevates their fusion. Mitochondrial dynamics exhibit an oscillatory pattern which matches the melatonin circadian secretory rhythm in pinealeocytes and probably in other cells. Recently, melatonin has been found to promote mitophagy and improve homeostasis of mitochondria.
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Mitochondria play an important role in the production, metabolism, and activity of melatonin.
“Recently obtained results indicate that mitochondria play an important role in the production, metabolism, and activity of melatonin (Tan et al. 2016; Tan and Reiter 2019).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Tan et al. 2016
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Self-citationEvidence for the Benefits of Melatonin in Cardiovascular Disease
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Self-citationMelatonin: A mitochondrial resident with a diverse skill set
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Self-citationMelatonin and Cancer: A Polyhedral Network Where the Source Matters
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Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed
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Melatonin, mitochondria, and the cancer cell
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Diabetes mellitus and melatonin: Where are we?
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Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue
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Self-citationAboTaleb, H. A., & Alghamdi, B. S. A. (2019) · Journal of Molecular Neuroscience · doi:10.1007/s12031-019-01425-6 · Cited by 53 · see citing works
The role of melatonin in targeting cell signaling pathways in neurodegeneration
Shukla, M., Chinchalongporn, V., Govitrapong, P., & Reiter, R. J. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14005 · Cited by 51 · see citing works
Self-citationNeuro-Inflammation Modulation and Post-Traumatic Brain Injury Lesions: From Bench to Bed-Side
Jacquens, A., Needham, E., Zanier, E. R., Degos, V., Gressèns, P., & Menon, D. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911193 · Cited by 51 · see citing works
- Authors
- Tan, D.-X., Manchester, L., Qin, L., & Reiter, R.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Tan, Dun-Xian
- Reiter, Russel
- ORCID
- Reiter, Russel
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2016-12-16
- Volume
- 17
- Issue
- 12
- Pages
- 2124
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5187924
- OpenAlex
- W2563008150
- Cited by
- 402
- References
- 206
- Citations by year
- 2026: 23 · 2025: 38 · 2024: 51 · 2023: 51 · 2022: 46 · 2021: 50 · 2020: 43 · 2019: 33 · 2018: 33 · 2017: 32
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- melatonin, mitochondrial targeting, mitochondrial protection, mitochondrial dynamics, mitochondrial fission and fusion, mitochondrial biogenesis, mitochondrial permeability transition pore, uncoupling proteins, reactive oxygen species scavenging, mitochondrial membrane potential, mitophagy, acetyltransferase, oocytes, pinealocytes, circadian rhythm
- MeSH terms
- Mitochondrial Uncoupling Proteins, Mitochondrial Permeability Transition Pore, Animals, Antioxidants, Circadian Rhythm, Enzyme Activation, Humans, Melatonin, Mitochondria, Plants, Reactive Oxygen Species, Mitochondrial Membrane Transport Proteins, Membrane Potential, Mitochondrial, Mitochondrial Dynamics, Mitophagy
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