Melatonin Facts: Musing With the Concept “Melatonin Travels Freely Through Biological Membranes”

Melatonin has been shown to travel freely through biological membranes. The consequences of this demonstration have been largely underestimated these past years. In particular, the behavior of melatonin during the preparation of samples from organs (ex vivo), from cells (in cellulo), or subcellular compartment(s) has been experimentally ignored. Melatonin is not retained in samples but can diffuse immediately outside those samples. Similarly, melatonin cannot be "trapped" in membrane-based organelles like mitochondria, nucleus, ER/Golgi, or lipid droplets of any sort. Consequently, existing data should be carefully reinterpreted, and future experiments should take the fact of melatonin diffusion into account, in particular when trying to provide convincing experimental evidence for local production of melatonin in cells and organelles outside of the pineal gland and the retina.