SCIENTIFIC MECHANISMS

Newer data indicate that the mitochondria are pivotal for several aspects of melatonin: its production, metabolism, and activity through receptors (1). Rather than respond to the signals of the light/dark cycle or the pineal gland, the mitochondria can induce the production of melatonin based on intracellular need. Levels of melatonin are known to be higher in mitochondria compared with blood levels, most likely due to the greater antioxidant requirements...

Numerous studies have identified melatonin as a powerful free-radical scavenger with potential protective properties against neurodegenerative disorders, epilepsy, and certain cancers. Recent in vitro and in vivo studies have continued to fortify the foundational aspects established over the past decades that would attest to melatonin’s roles in antioxidant defense, oxidative stress reduction, and anti-inflammatory processes (1,2). Notably, as stated above, it is a highly efficient antioxidant as one molecule of melatonin can scavenge multiple (~10) reactive oxygen and nitrogen species through a cascading mechanism related to its secondary, tertiary, and even quaternary metabolites (3,4)....

The broader picture of mental health, specifically depression, has been correlated with melatonin levels. While low serotonin levels are known to be consistent with clinical depression, low melatonin levels also appear to have a significant connection. Low levels of melatonin may trigger an upregulation in the kynurenine pathway, and kynurenine production, as well as trigger the aryl hydrocarbon receptor (AhR) located on the outer membrane of the mitochondria (1–5)....

Two types of cells are responsible for the production of melatonin: pinealocytes and enterochromaffin cells. Pinealocytes are located in the pineal gland within the brain. Enterochromaffin cells are located on the surface of the entire gastrointestinal (GI) tract, with high concentrations in the mucosal lining of the GI tract. Pinealocytes are affected by light and dark; exposure to light suppresses melatonin production and release from the pinealocytes, while darkness (when registered by the retina) increases melatonin production and release into the bloodstream starting with vessels in the brain...

Over the past few decades, there has been groundbreaking exploration within cell biology into the topic of the structures within the cell and how they organize and function, which ultimately has implications for disease states [1]. Within the cell, there are structures bound with a membrane like the mitochondria or the nucleus. Separate from these membrane-bound structures within the cell, there are areas of the cell that are phase separated from the membrane, like islands. They are referred to as liquid-like membrane-less organelles, or MLOs [2]...