Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW8O30} Determined by Single-Cell Proteomics Analysis

The 10-nuclear heteroatom cluster modified {SbW8O30} was successfully synthesized and exhibited inhibitory activity (IC50=0.29 mu M). Based on proteomics analysis, Na4Ni2Sb2W2-SbW8 inhibited ATP production by affecting the expression of 16 related proteins, hindering metabolic functions in vivo and cell proliferation due to reactive oxygen species (ROS) stress. In particular, the low expression of FAD/FMN-binding redox enzymes (relative expression ratio of the experimental group to the control=0.43843) could be attributed to the redox mechanism of Na4Ni2Sb2W2-SbW8, which was consistent with the effect of polyoxometalates (POMs) and FMN-binding proteins on ATP formation. An electrochemical study showed that Na4Ni2Sb2W2-SbW8 combined with FMN to form Na4Ni2Sb2W2-SbW8-2FMN complex through a one-electron process of the W atoms. Na4Ni2Sb2W2-SbW8 acted as catalase and glutathione peroxidase to protect the cell from ROS stress, and the inhibition rates were 63.3 % at 1.77 mu M of NADPH and 86.06 % at 10.62 mu M of 2-hydroxyterephthalic acid. Overall, our results showed that POMs can be specific oxidative/antioxidant regulatory agents.

Automated summary

The modified 10-nuclear heteroatom cluster exhibited inhibitory activity, affecting ATP production through modulation of protein expression related to metabolism. It acted as a protective agent against ROS stress by functioning as catalase and glutathione peroxidase, and showed potential as specific oxidative/antioxidant regulatory agents.