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Updated: Aug 2, 2025
10:39
Visualization of ATP Synthase Dimers in Mitochondria by Electron Cryo-tomography
Published on: September 14, 2014
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Spatial and temporal dynamics of ATP synthase from mitochondria toward the cell surface
Yi-Wen Chang1, T Tony Yang2,3, Min-Chun Chen1
1Department of Life Science, Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, 106, Taiwan.
Communications Biology
|April 18, 2023
Summary
Ectopic ATP synthase (eATP synthase) is transported from mitochondria to the cancer cell surface via microtubules, involving DRP1 and KIF5B. This process, involving membrane fusion, is crucial for tumor progression and offers a potential therapeutic target.
Area of Science:
- Cell Biology
- Cancer Biology
- Molecular Oncology
Background:
- Ectopic ATP synthase (eATP synthase) on cancer cell surfaces generates extracellular ATP, supporting tumor microenvironments.
- The transport mechanism of eATP synthase from intracellular compartments to the cell surface is largely unknown.
- Understanding eATP synthase trafficking is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To elucidate the intracellular transport pathway of ATP synthase complex to the cancer cell surface.
- To identify key molecular players involved in eATP synthase trafficking.
- To investigate the mechanism of eATP synthase anchoring on the cell surface.
Main Methods:
- Spatial proteomics, interaction proteomics, and transcriptomics analyses were employed.
- Super-resolution imaging and real-time fusion assays in live cells were utilized.
- Investigated the roles of dynamin-related protein 1 (DRP1) and kinesin family member 5B (KIF5B).
Main Results:
- ATP synthase complex is assembled in mitochondria before transport.
- Transport to the cell surface occurs along microtubules, mediated by DRP1 and KIF5B.
- Mitochondrial and plasma membrane fusion anchors eATP synthase on the cell surface.
Conclusions:
- A detailed blueprint for eATP synthase trafficking has been established.
- The findings provide insights into the dynamics of tumor progression and extracellular ATP generation.
- This study identifies a novel mechanism for cell surface protein localization with therapeutic implications.
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