Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW8 O30 } Determined by Single-Cell Proteomics Analysis

Abstract

The 10-nuclear heteroatom cluster modified {SbW₈ O₃₀ } was successfully synthesized and exhibited inhibitory activity (IC₅₀ =0.29 μM). Based on proteomics analysis, Na₄ Ni₂ Sb₂ W₂ -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 Na₄ Ni₂ Sb₂ W₂ -SbW₈ , which was consistent with the effect of polyoxometalates (POMs) and FMN-binding proteins on ATP formation. An electrochemical study showed that Na₄ Ni₂ Sb₂ W₂ -SbW₈ combined with FMN to form Na₄ Ni₂ Sb₂ W₂ -SbW₈ -2FMN complex through a one-electron process of the W atoms. Na₄ Ni₂ Sb₂ W₂ -SbW₈ acted as catalase and glutathione peroxidase to protect the cell from ROS stress, and the inhibition rates were 63.3 % at 1.77 μM of NADPH and 86.06 % at 10.62 μM of 2-hydroxyterephthalic acid. Overall, our results showed that POMs can be specific oxidative/antioxidant regulatory agents.

Keywords: ATP synthesis; oxidative stress; polyoxometalates; single-cell organisms.