Evidence map›Paper›PMID 28880942›Full record

ArticlePloS one2017

Live-cell imaging to measure BAX recruitment kinetics to mitochondria during apoptosis.

Margaret E Maes, Cassandra L Schlamp, Robert W Nickells

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  7. Review
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  9. BCLXCell death & disease · 2021
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  11. Review
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  13. [Effect of enhancer of zeste homolog 2 inhibitor GSK126 on the proliferation and apoptosis of tongue squamous cell carcinoma].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2020
    Article
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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

3 authors at 1 institution in 1 country.

Margaret E MaesDepartment of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
Cassandra L SchlampDepartment of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
Robert W NickellsDepartment of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.ORCID http://orcid.org/0000-0002-2998-5494
University of Wisconsin–Madison · US

Funding

UW Vision Research Core - Administrative CoreP30EY016665 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI ROBERT W NICKELLS · 2005 to 2026
$12.6M
The molecular mechanism of retinal ganglion cell deathR01EY012223 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI NICKELLS, ROBERT W · 2005 to 2017
$6.3M
Graduate Training In Cellular And Molecular Pathogenesis Of Human DiseasesT32GM081061 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FABRY, ZSUZSANNA · 2010 to 2019
$1.8M
NEI NIH HHS P30 EY016665NEI NIH HHS R01 EY012223NIGMS NIH HHS T32 GM081061
6 · The paper itself

Abstract

The pro-apoptotic BCL2 gene family member, BAX, plays a pivotal role in the intrinsic apoptotic pathway. Under cellular stress, BAX recruitment to the mitochondria occurs when activated BAX forms dimers, then oligomers, to initiate mitochondria outer membrane permeabilization (MOMP), a process critical for apoptotic progression. The activation and recruitment of BAX to form oligomers has been studied for two decades using fusion proteins with a fluorescent reporter attached in-frame to the BAX N-terminus. We applied high-speed live cell imaging to monitor the recruitment of BAX fusion proteins in dying cells. Data from time-lapse imaging was validated against the activity of endogenous BAX in cells, and analyzed using sigmoid mathematical functions to obtain detail of the kinetic parameters of the recruitment process at individual mitochondrial foci. BAX fusion proteins behave like endogenous BAX during apoptosis. Kinetic studies show that fusion protein recruitment is also minimally affected in cells lacking endogenous BAK or BAX genes, but that the kinetics are moderately, but significantly, different with different fluorescent tags in the fusion constructs. In experiments testing BAX recruitment in 3 different cell lines, our results show that regardless of cell type, once activated, BAX recruitment initiates simultaneously within a cell, but exhibits varying rates of recruitment at individual mitochondrial foci. Very early during BAX recruitment, pro-apoptotic molecules are released in the process of MOMP, but different molecules are released at different times and rates relative to the time of BAX recruitment initiation. These results provide a method for BAX kinetic analysis in living cells and yield greater detail of multiple characteristics of BAX-induced MOMP in living cells that were initially observed in cell free studies.

Indexed as

ApoptosisApoptosis Inducing FactorApoptosis Regulatory Proteinsbcl-2-Associated X ProteinCell LineComputational BiologyCytochromes cFluorescent Antibody TechniqueHeLa CellsHumansIntracellular Signaling Peptides and ProteinsKineticsMitochondriaMitochondrial ProteinsPlasmidsAIFM1 protein, humanApoptosis Inducing FactorApoptosis Regulatory Proteinsbcl-2-Associated X ProteinCytochromes cDIABLO protein, humanIntracellular Signaling Peptides and ProteinsMitochondrial Proteins

Identifiers

PMID28880942
PMCPMC5589231
OpenAlexW2751850629

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.