Melanocytes are distributed in the epidermis, hair follicles, choroid, iris, inner ear, and other tissues ( Dubey & Roulin, 2014).

Melanin pigments in vertebrates are produced in melanocytes within membrane-bound organelles termed melanosomes thereafter, the melanosomes in the hair follicle and epidermal melanocytes are transferred to the surrounding keratinocytes leading to a diverse range of hair and skin colors ( Del Bino et al., 2015 Delevoye, 2014 Lin & Fisher, 2007 Ohbayashi & Fukuda, 2020 Sturm, 2009). Melanin pigments, widely distributed in vertebrates, are composed of insoluble brown to black pigments termed eumelanin (EM) and alkali-soluble yellow to reddish-brown pigments termed pheomelanin (PM) ( Ito & Wakamatsu, 2003, 2008). Here, we focused on various factors affecting mixed melanogenesis including (1) chemical regulation of melanin synthesis, (2) melanosomal pH regulation during normal melanogenesis and effect on mixed melanogenesis, and (3) mechanisms of melanosomal pH control (proton pumps, channels, transporters, and signaling pathways). Due to the differential sensitivity of the eumelanin and pheomelanin synthetic pathways to pH, melanosomal pH likely plays a major role in mixed melanogenesis. Most natural melanin pigments in animals consist of both eumelanin and pheomelanin in varying ratios, and thus, their combined synthesis is called “mixed melanogenesis.” Gene expression is an established mechanism for controlling melanin synthesis however, there are multiple factors that affect melanin synthesis besides gene expression. The diversity of pigmentation in vertebrates is mainly attributed to the quantity and ratio of eumelanin and pheomelanin synthesis.

Melanins are widely distributed in animals and plants in vertebrates, most melanins are present on the body surface.

Skin and Blond by V.J. Chambers