Fig. 4: Mn²⁺ binding site is crucial for the protective function of SLC30A10.

a Proposed model for the Mn²⁺ transport mechanism of SLC30A10: The orientation and relative positions of helices and key residues are shown based on the structural data. Purple spheres represent Mn²⁺ ions. For clarity, only the transmembrane domain (TMD) of one protomer is shown. Mn²⁺ is attracted to a negatively charged cytoplasmic cavity (Red) and coordinated by D248, D40, N127, and S252. The ions are ultimately exported through an extracellular cavity, exiting the cell. b–e Statistical analysis of normalized Mn levels (b; n = 5), ROS levels (c; n = 3), mitochondrial membrane potential (d; n = 3) and ATP levels (e; n = 3) in the presence of 100 μM MnCl₂ for 24 h in SH-SY5Y cells. f, g Flow cytometry detection (f) and statistical analysis (g; n = 3) of cell survival by Annexin V / PI staining in SH-SY5Y cells. All bar graphs above represent mean ± SEM from three independent experiments. Statistical analysis was performed using one-way ANOVA with Dunnett’s multiple comparisons test (****p < 0.0001; ***p < 0.001; **p < 0.01; *p < 0.05; ns not significant).