Spatial and temporal dynamics of ATP synthase from mitochondria toward the cell surface

Ectopic ATP synthase complex (eATP synthase), located on cancer cell surface, has been reported to possess catalytic activity that facilitates the generation of ATP in the extracellular environment to establish a suitable microenvironment and to be a potential target for cancer therapy. However, the mechanism of intracellular ATP synthase complex transport remains unclear. Using a combination of spatial proteomics, interaction proteomics, and transcriptomics analyses, we find ATP synthase complex is first assembled in the mitochondria and subsequently delivered to the cell surface along the microtubule via the interplay of dynamin-related protein 1 (DRP1) and kinesin family member 5B (KIF5B). We further demonstrate that the mitochondrial membrane fuses to the plasma membrane in turn to anchor ATP syntheses on the cell surface using super-resolution imaging and real-time fusion assay in live cells. Our results provide a blueprint of eATP synthase trafficking and contribute to the understanding of the dynamics of tumor progression. The ectopic ATP synthase complex is assembled in mitochondria and transported to the cell surface via microtubules and dynamin-related protein 1 and kinesin KIF5B.

Automated summary

The ectopic ATP synthase complex, which is located on the surface of cancer cells, plays a role in generating ATP in the extracellular environment and has potential as a target for cancer therapy. Through various proteomics and transcriptomics analyses, researchers have discovered that the ATP synthase complex is first assembled in mitochondria and then transported to the cell surface via microtubules and dynamin-related protein 1 (DRP1) and kinesin family member 5B (KIF5B) interactions. The fusion of mitochondrial membrane to the plasma membrane anchors the ATP synthase on the cell surface, as demonstrated by super-resolution imaging and real-time fusion assays in live cells. These findings provide insight into the trafficking of ectopic ATP synthase and contribute to our understanding of tumor progression dynamics.