Single-Mitochondrion ATP Profiling Directs Discovery of Targetable OXPHOS Dependency in Cancers.

Xu Xiao, Cheng Lu, Hao Chen, Jing Zhou, Yunyun Hu, Haonan Di, Guoqiang Su, Xiaomei Yan

Abstract read

In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

Special Issue "Flow Cytometry: Applications and Challenges".International journal of molecular sciences · 2026
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Xu XiaoDepartment 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.ORCID https://orcid.org/0009-0007-4213-7303

Cheng LuDepartment 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.

Hao ChenDepartment 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.

Jing ZhouDepartment 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.

Yunyun HuDepartment 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.

Haonan DiDepartment 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.

Guoqiang SuDepartment of Colorectal Tumor Surgery, Xiamen Key Laboratory of Early Cancer Diagnosis and Treatment, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.

Xiaomei YanDepartment 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.ORCID https://orcid.org/0000-0002-7482-6863

Funding

National Key R&D Program of China 2021YFA0909400National Key R&D Program of China 2024YFA1108700National Natural Science Foundation of China 21934004National Natural Science Foundation of China 32450337

6 · The paper itself

Abstract

Mitochondrial adenosine triphosphate (mitoATP) serves as the primary bioenergetic currency for oxidative phosphorylation (OXPHOS)-driven malignancies, yet its precise organelle-level quantification remains challenging due to mitochondrial heterogeneity and cytosolic interference. Herein, we report MitoATP-nFCM, a nano-flow cytometry platform enabling single-mitochondrion ATP measurement via simultaneous fluorescence and side scatter detection. We uncover 1.7-1.9-fold higher ATP levels in isolated mitochondria from breast (MCF-7, MDA-MB-231) and colon (HCT-15, HCT-116) cancer cells than in their normal counterparts. Single-organelle analysis further reveals coordinated metabolic reprogramming in cancer mitochondria, featuring elevated membrane potential, increased ATP synthase expression, and reduced hexokinase 2 levels, demonstrating their OXPHOS-dominant bioenergetic phenotype that contrasts with classical Warburg-effect expectations. Furthermore, we establish a screening strategy to identify highly potent cancer-selective inhibitors targeting mitochondrial metabolism. We find that bedaquiline (ATP synthase inhibitor) outperforms oligomycin A in specificity, VLX600 (electron transport chain inhibitor) shows superior selectivity to rotenone/metformin, and CPI-613 (tricarboxylic acid cycle blocker) surpasses other glutaminase inhibitors. MitoATP-nFCM establishes a quantitative single-organelle platform that profiles elevated mitoATP levels in cancer cells and enables precision screening of OXPHOS-targeting inhibitors.

Indexed as

Adenosine TriphosphateMitochondriaNeoplasmsOxidative PhosphorylationCell Line, TumorDiarylquinolinesFemaleFlow CytometryHumansMetabolic ReprogrammingAdenosine TriphosphatebedaquilineDiarylquinolinescancer vulnerabilitymitochondrial ATPmitochondrial metabolismprecision cancer therapysingle‐organelle analysis

Identifiers

PMID41684301

DOI10.1002/advs.202513341

PMCPMC13073232

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.