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Single-Mitochondrion ATP Profiling Directs Discovery of Targetable OXPHOS Dependency in Cancers
Xu Xiao1, Cheng Lu1, Hao Chen1
1Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 13, 2026
Summary
Cancer cells exhibit higher mitochondrial ATP levels than normal cells, revealed by a new nano-flow cytometry method. This platform aids in developing targeted therapies by screening mitochondrial metabolism inhibitors.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Mitochondrial adenosine triphosphate (mitoATP) is crucial for cancer cell energy, but its measurement is difficult.
- Cancer cells often rely on oxidative phosphorylation (OXPHOS), contrary to the Warburg effect.
- Mitochondrial heterogeneity and cytosolic interference complicate organelle-level ATP quantification.
Purpose of the Study:
- To develop a novel platform for single-mitochondrion ATP measurement.
- To quantify mitoATP levels in cancer versus normal cells.
- To establish a screening strategy for cancer-selective mitochondrial metabolism inhibitors.
Main Methods:
- Developed MitoATP-nFCM, a nano-flow cytometry platform for single-mitochondrion ATP measurement.
- Utilized simultaneous fluorescence and side scatter detection.
- Analyzed ATP levels, membrane potential, ATP synthase, hexokinase 2, and screened inhibitors.
Main Results:
- MitoATP-nFCM enabled precise single-organelle ATP quantification.
- Cancer cell mitochondria showed 1.7-1.9 fold higher ATP levels than normal cells.
- Identified specific OXPHOS inhibitors: bedaquiline, VLX600, and CPI-613.
Conclusions:
- MitoATP-nFCM is a valuable tool for profiling mitochondrial bioenergetics in cancer.
- Cancer cells exhibit an OXPHOS-dominant phenotype with reprogrammed mitochondrial metabolism.
- The platform facilitates precision screening of novel mitochondrial metabolism inhibitors for cancer therapy.
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