Evidence map›Paper›PMID 33561427›Full record

ArticleCell metabolism2021

Transient phases of OXPHOS inhibitor resistance reveal underlying metabolic heterogeneity in single cells.

Nont Kosaisawe, Breanne Sparta, Michael Pargett, Carolyn K Teragawa, John G Albeck

Open access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.7field-weighted citation impact, top 2% of its field
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

31 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
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  3. Specific FbioRxiv : the preprint server for biology · 2026
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  20. CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    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

5 authors at 1 institution in 1 country.

Nont KosaisaweDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Breanne SpartaDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Michael PargettDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Carolyn K TeragawaDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
John G AlbeckDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA. Electronic address: jgalbeck@ucdavis.edu.
University of California, Davis · US

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura Marcu · 2002 to 2026
$84.9M
The role of dynamics in defining the limits of normal developmental signaling.R01GM115650 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ALBECK, JOHN G. · 2016 to 2021
$1.8M
NCI NIH HHS P30 CA093373NIGMS NIH HHS R01 GM115650
6 · The paper itself

Abstract

Cell-to-cell heterogeneity in metabolism plays an unknown role in physiology and pharmacology. To functionally characterize cellular variability in metabolism, we treated cells with inhibitors of oxidative phosphorylation (OXPHOS) and monitored their responses with live-cell reporters for ATP, ADP/ATP, or activity of the energy-sensing kinase AMPK. Across multiple OXPHOS inhibitors and cell types, we identified a subpopulation of cells resistant to activation of AMPK and reduction of ADP/ATP ratio. This resistant state persists transiently for at least several hours and can be inherited during cell divisions. OXPHOS inhibition suppresses the mTORC1 and ERK growth signaling pathways in sensitive cells, but not in resistant cells. Resistance is linked to a multi-factorial combination of increased glucose uptake, reduced protein biosynthesis, and G0/G1 cell-cycle status. Our results reveal dynamic fluctuations in cellular energetic balance and provide a basis for measuring and predicting the distribution of cellular responses to OXPHOS inhibition.

Indexed as

Adenosine DiphosphateAdenosine TriphosphateAMP-Activated Protein KinasesAntineoplastic AgentsCell LineExtracellular Signal-Regulated MAP KinasesG1 PhaseGlucoseHumansMechanistic Target of Rapamycin Complex 1Oxidative PhosphorylationProtein BiosynthesisSignal TransductionAdenosine DiphosphateAdenosine TriphosphateAMP-Activated Protein KinasesAntineoplastic AgentsExtracellular Signal-Regulated MAP KinasesGlucoseMechanistic Target of Rapamycin Complex 1adenosine mono-phosphate-regulated protein kinaseAKTelectron transport chainFRETinsulin signalingmammalian target of rapamycinmetabolic cycleoligomycinoscillationPI3Ktranslation regulation

Identifiers

PMID33561427
PMCPMC8005262
OpenAlexW3127540358

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.