Spatial and temporal dynamics of ATP synthase from mitochondria toward the cell surface
Journal
Communications biology
Journal Volume
6
Journal Issue
1
Pages
Article number 427
Date Issued
2023-04-18
Author(s)
Chang, Yi-Wen
Tony Yang, T
Chen, Min-Chun
Liaw, Y-Geh
Yin, Chieh-Fan
Lin-Yan, Xiu-Qi
Huang, Ting-Yu
Hou, Jen-Tzu
Hung, Yi-Hsuan
Hsu, Chia-Lang
Huang, Hsuan-Cheng
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.
Subjects
AXONAL-TRANSPORT; PLASMA-MEMBRANE; ANGIOGENESIS INHIBITOR; MALATE-DEHYDROGENASE; THERAPEUTIC TARGET; CITRATE SYNTHASE; FISSION; FUSION; DRP1; EXPRESSION
SDGs
Publisher
NATURE PORTFOLIO
Type
journal article