Fig. 5: High atomic vacancy MoS₂ decreases oxidative stress and enhances mitochondrial bioenergetics.

A The effect of MoS₂ on OCR was determined in C2C12 cells treated with different concentrations of MoS₂ (1:6) (0, 10 and 25 µg/mL). A concentration-dependent increase in spare respiratory capacity was observed, indicating the ability of MoS₂ to activate mitochondrial respiration machinery. (n = 3 biological replicates). B Evaluation of ATP levels in cells treated with MoS₂ (1:6) suggests a marked increase in ATP levels, compared to untreated hMSCs. (n = 4 biological replicates). C Effect of MoS₂ on mitochondrial membrane potential. Cells treated with MoS₂ (1:6) showed no significant changes in mitochondrial membrane potential as compared to untreated cells. Cell number variation was normalized using nuclear stain (DAPI). (n = 4 biological replicates). D The amount of intracellular ROS is determined before and after treatment with MoS₂ (1:6). MoS₂ treatment significantly suppressed ROS production. (n = 3 biological replicates). E The amount of mitochondrial ROS is determined using MitoSox before and after treatment with MoS₂ nanoflowers (1:6). MoS₂ treatment significantly suppressed mitochondrial ROS production. (n = 3 biological replicates). F RNA-seq data demonstrates the upregulation of multiple genes related to antioxidant activity (GO: 0016209). G PGC-1α expression in C2C12 transduced with either empty vector (pLKO) or shRNA targeting PGC-1α (n = 3 biological replicates). H Evaluation of relative mitochondrial copy number in transduced cells following treatment with MoS₂ for 72 h. (n = 3 biological replicates). I Mitochondrial copy number in hMSCs following treatment with N-acetyl cysteine (NAC), resveratrol, and vacancy-rich MoS₂. Cells were treated with either NAC (3 mM), resveratrol (25 µm), or MoS₂ (1:6) (25 µg/mL) for 72 h. (n = 3 biological replicates). J Proposed mechanism of action of MoS₂ with high atomic vacancies on triggering mitochondrial biogenesis. It is expected that atomic vacancies of MoS₂ exhibit free radical scavenging activity through rapid reactions with reactive oxygen species (ROS), including hydrogen peroxide (H₂O₂), superoxide anions (O₂^•−), and hydroxyl radicals (^•OH). Reduction in intracellular ROS due to the presence of atomic vacancies on MoS₂ is expected to trigger the SIRT1/PGC1α/NRF2 pathway. For (A), (B), (C), (D), (E), (G), (H), and (I), data represented as mean ± SD. For (C), (D), (E), (I) Statistical significance was determined using one way ANOVA with post hoc Tukey test. For (G), (H) Statistical significance was determined using a two-tailed student t test. For all data sets n.s. p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.