Physiological roles of zinc transporters: molecular and genetic importance in zinc homeostasis

Zinc (Zn) is an essential trace mineral that regulates the expression and activation of biological molecules such as transcription factors, enzymes, adapters, channels, and growth factors, along with their receptors. Zn deficiency or excessive Zn absorption disrupts Zn homeostasis and affects growth, morphogenesis, and immune response, as well as neurosensory and endocrine functions.

Zinc homeostasis is essential for life:

Bioinformatics analysis of the human genome reveals that zinc (Zn) can bind ~10% of all of the proteins found in the human body [12]. This remarkable finding highlights the physiological importance of Zn in molecules involved in cellular processes. Zn is required for the normal function of numerous enzymes, transcriptional factors, and other proteins [3,4,5,6]. These proteins can potentially interact with Zn through specific regions such as Zn-finger domains, LIM domains, and RING finger domains. The skeletal muscles and bones serve as major tissue reservoirs for Zn [78] (Fig. 1) but cannot store more Zn than the body needs. Therefore, we must take in Zn daily from our diet to maintain proper Zn-related cellular processes. While the toxicity of Zn is quite low, and it is generally non-harmful, a deficiency or excess of Zn can cause severe symptoms [4].Zn deficiency causes eye and skin lesions, hair loss, immune dysfunction, taste abnormalities, and growth retardation, and excessively high Zn exhibits its toxicity as nausea, vomiting, fever, and headaches [9]. Symptoms of Zn deficiency are improved by Zn supplementation [4], confirming that Zn is an essential trace mineral and that Zn homeostasis is a crucial physiological process [10,11,12,13,14,15].

Zn storage and distribution in the body. Dietary Zn is absorbed from the small intestine and distributed to the organs. Bones and skeletal muscles act as major Zn reservoir tissues