Figure 3.

Mn²⁺ and Zn²⁺ homeostasis. (A) Representative scheme of Mn²⁺ and Zn²⁺ transport and cellular compartments. Blue arrows represent Zn²⁺-transporting carriers (SLC39A1, SLC30A3), orange arrows represent Mn²⁺-transporting carriers (SLC39A14, SLC30A10). Double arrows represent proteins that transfer both Mn²⁺ and Zn²⁺ (SLC39A8, SLC40A1). In the cell, Zn²⁺ is distributed between metallothioneins, other proteins and GSH [84,85]. In the nuclei, Zn²⁺ binds MTF1 [25] and serves as a coordination metal for the majority of histone-modifying enzymes [112,113] and zinc finger transcription factors (ZFTFs) [114]. In turn, Mn²⁺ accumulates in heterochromatin [66]. Both Mn²⁺ and Zn²⁺ can accumulate in mitochondria [3,8], as well as in the Golgi apparatus and endoplasmic reticulum [10,11,115,116] (not shown). Both Mn²⁺ and Zn²⁺ can be sequestered in specific vesicles that can be released from the cell [9,26,27]. (B) Ion carriers transfer Mn²⁺ in mitochondria using Mfrn1 [117] and DMT1 [118], and in cellular vesicles by SLC30A10 [108]. In turn, Zn²⁺ is accumulated in mitochondria by SLC25A25 and exerted by SLC30A9 [8,23]. In vesicles, Zn²⁺ is accumulated by SLC30A3-SLC30A10 heterodimer [107] and exerted by SLC39A13 [119].