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Abstract
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.
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1 National Taiwan University, Department of Life Science, Institute of Molecular and Cellular Biology, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241)
2 National Taiwan University, Department of Electrical Engineering, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241)
3 National Taiwan University, Department of Life Science, Institute of Molecular and Cellular Biology, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); National Taiwan University Hospital, Department of Medical Research, Taipei, Taiwan (GRID:grid.412094.a) (ISNI:0000 0004 0572 7815)
4 National Yang Ming Chiao Tung University, Institute of Biomedical Informatics, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017)
5 National Taiwan University, Department of Life Science, Institute of Molecular and Cellular Biology, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); National Taiwan University, Center for Computational and Systems Biology, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241)