• Phomoxanthone A Targets ATP Synthase

      Ali, Rameez; Parelkar, Sangram S; Thompson, Paul R; Mitroka-Batsford, Susan; Yerramilli, Siddartha; Scarlata, Suzanne F; Mistretta, Katelyn S; Coburn, Jeannine M; Mattson, Anita E (2022-09-09)
      Phomoxanthone A is a naturally occurring molecule and a powerful anti-cancer agent, although its mechanism of action is unknown. To facilitate the determination of its biological target(s), we used affinity-based labelling using a phomoxanthone A probe. Labelled proteins were pulled down, subjected to chemoproteomics analysis using LC-MS/MS and ATP synthase was identified as a likely target. Mitochondrial ATP synthase was validated in cultured cells lysates and in live intact cells. Our studies show sixty percent inhibition of ATP synthase by 260 μM phomoxanthone A.