The DOI matches its Crossref record; 158 of the 168 references it cites were found in a registry or an index.
Mitochondria: the birth place, battle ground and the site of melatonin metabolism in cells
Open accessAbstract
It was a surprising discovery when mitochondria, as the power houses of cells, were also found to synthesize the potent mitochondrial targeted antioxidant, melatonin. The melatonin synthetic enzyme serotonin N-acetyltransferase (SNAT) was found in matrix and also in the intermembrane space of mitochondria. We hypothesize that the melatonin synthesis occurs in the matrix due to substrate (N-acetyl co-enzyme A) availability while the intermembrane space may serve as the recycling pool of SNAT to regulate the melatonin circadian rhythm. Another surprise was that the melatonin membrane receptors, including MT1 and MT2, were also present in mitochondria. The protective effects of melatonin against neuronal injury induced by brain ischemia/reperfusion were proven to be mainly mediated by mitochondrial melatonin receptors rather than the cell surface membrane receptors which is contrary to the classical principle. In addition, melatonin metabolic enzyme has also been identified in the mitochondria. This enzyme can convert melatonin to N-acetylserotonin to strengthen the antitumor effects of melatonin. Thus, mitochondria are the generator, battle ground and metabolic sites of melatonin. The biological significance of the strong association between mitochondria and melatonin should be intensively investigated.
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“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 and Reiter 2019
In the citing paper
“Newer data indicate that the mitochondria are pivotal for several aspects of melatonin: its production, metabolism, and activity through receptors [35].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [35]
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Cites
1 retracted
Kashani, I. R., Rajabi, Z., Akbari, M., Hassanzadeh, G., Mohseni, A., Eramsadati, M. K., Rafiee, K., Beyer, C., Kipp, M., & Zendedel, A. (2014) · Experimental Brain Research · doi:10.1007/s00221-014-3946-5 · Cited by 56 · cited 1×
“For post-miotic cells including neurons, myocardial cells and muscle most of the time melatonin inhibits mitochondrial fission and promotes fusion (151-153).”
BackgroundRetractedPineal Melatonin: Cell Biology of Its Synthesis and of Its Physiological Interactions*
REITER, R. J. (1991) · Endocrine Reviews · doi:10.1210/edrv-12-2-151 · Cited by 2,192 · cited 1×
“However, the sole starting material of melatonin synthesis in vertebrates is tryptophan (34), an essential amino acid.”
BackgroundSelf-citationTan, D., Manchester, L. C., Terron, M. P., Flores, L. J., & Reiter, R. J. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00407.x · Cited by 1,601 · cited 15×
“The high mΔψ decreases the electron flow in the ETC and mitochondria enter the stagnation status, which results in electron leakage from the ETC and forms ROS.”
BackgroundInfluentialSelf-citationCommon Principles of Protein Translocation Across Membranes
Schatz, G., & Dobberstein, B. (1996) · Science · doi:10.1126/science.271.5255.1519 · Cited by 1,116 · cited 1×
“The mitochondrial-targeted transient peptides are both necessary and sufficient for import of the proteins into mitochondria that contain them (45, 46).”
BackgroundRole of mitochondrial ROS in the brain: from physiology to neurodegeneration
Angelova, P. R., & Abramov, A. Y. (2018) · FEBS Letters · doi:10.1002/1873-3468.12964 · Cited by 789
Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism
Tan, D.-X., Manchester, L., Esteban-Zubero, E., Zhou, Z., & Reiter, R. (2015) · Molecules · doi:10.3390/molecules201018886 · Cited by 719 · cited 1×
“was discussed in detail by two groups (60, 63).”
BackgroundSelf-citationMelatonin membrane receptors in peripheral tissues: Distribution and functions
Slominski, R. M., Reiter, R. J., Schlabritz‐Loutsevitch, N., Ostrom, R. S., & Slominski, A. T. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.01.004 · Cited by 701 · cited 1×
“It is a little surprising that the melatonin plasma membrane receptor, particularly MT1, is present also in the mitochondria since this G protein-coupled receptor (GPCR) is classically characterized as cell-surface receptor which transmits extracellular signals into cells (161, 162).”
BackgroundSelf-citationMelatonin: The chemical expression of darkness
Reiter, R. J. (1991) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(91)90087-9 · Cited by 634 · cited 1×
“In vertebrates, melatonin also serves as the signalling molecule to transduce environmental photoperiodic information to their neuroendocrine system (13-15).”
BackgroundSelf-citationMitochondrial uncoupling, ROS generation and cardioprotection
Cadenas, S. (2018) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2018.05.019 · Cited by 591 · cited 1×
“In this way, melatonin accelerates the electron flow in the ETC and reduces the electron leakage thereby avoiding ROS formation (141).”
BackgroundTan, D. X., Manchester, L. C., Liu, X., Rosales‐Corral, S., Acuña-Castroviejo, D., & Reiter, R. J. (2012) · Journal of Pineal Research · doi:10.1111/jpi.12026 · Cited by 584 · cited 4×
“Thus, melatonin is referred as the mitochondrial targeted antioxidant (5, 89-91).”
BackgroundInfluentialSelf-citation
Cited by
Sorted by citations
Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638
Singh, S., & Singh, T. G. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200207120949 · Cited by 307
“Mn-SOD is an important anti-oxidant enzyme essential for the protection of cellular damage [79].”
BackgroundMelatonin metabolism, signaling and possible roles in plants
Back, K. (2020) · The Plant Journal · doi:10.1111/tpj.14915 · Cited by 279
Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging
Tamura, H., Jozaki, M., Tanabe, M., Shirafuta, Y., Mihara, Y., Shinagawa, M., Tamura, I., Maekawa, R., Sato, S., Taketani, T., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031135 · Cited by 237
Self-citationMelatonin: Roles in influenza, Covid‐19, and other viral infections
Anderson, G., & Reiter, R. J. (2020) · Reviews in Medical Virology · doi:10.1002/rmv.2109 · Cited by 212
“melatonin to be intimately associated with mitochondrial function, and thereby with immune system regulation.(6) The interactions of our “bacterial-driven” coexistence with viruses have provided a “War of the Worlds” from which plant and animal evolution have emerged, and in which evolution has acted to tolerate and l…”
BackgroundSelf-citation
Metadata
- Authors
- Tan, D.-X., & Reiter, R. J.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- ORCID
- Reiter, Russel. J.
- Venue
- Melatonin Research
- Publisher
- ST Bio-life
- Published
- 2019-02-28
- Volume
- 2
- Issue
- 1
- Pages
- 44-66
- ISSN
- 2641-0281 (ISSN-L)
- OpenAlex
- W2919912171
- Cited by
- 172
- References
- 168
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 12 · 2023: 20 · 2022: 20 · 2021: 38 · 2020: 41 · 2019: 32
- FWCI
- 18.08
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Melatonin Research (publishedVersion, cc-by)
- 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 synthesis, mitochondria, serotonin N-acetyltransferase, mitochondrial matrix, intermembrane space, melatonin receptors, MT1 receptor, MT2 receptor, cerebral ischemia-reperfusion injury, neuronal injury, N-acetylserotonin, melatonin metabolism, circadian rhythm, anticancer activity
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