Figure 6
From: hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer
The integrated role of ZIP1, zinc, and citrate metabolism in the pathogenesis of prostate malignancy. The normal glandular epithelial cell expresses ZIP1 that permits zinc accumulation, which inhibits citrate oxidation and terminal respiration. Citrate accumulates and coupled ATP production is reduced. A genetic transformation results in a neoplastic cell with potential malignant capability. ZIP1 expression is silenced by epigenetic factors which eliminate Zip1 transporter and accumulation of zinc in the premalignant cell. The level of cellular zinc decreases which removes the inhibitory effects on citrate oxidation and terminal oxidation. The Krebs cycle is functional and coupled ATP production is increased. The malignant cell is metabolically and bioenergetically capable of manifesting its malignant potential. Additionally, the growth inhibitory effect of zinc is removed, which allows growth and progression of the malignant cell.