Evidence map›Paper›PMID 27763642›Full record

ArticleCell death & disease2016

Bcl-2 proteins bid and bax form a network to permeabilize the mitochondria at the onset of apoptosis.

Robert F Gahl, Pallavi Dwivedi, Nico Tjandra

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

34 citing papers in PubMed, 64 citations in OpenAlex.

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  11. Dynamic features of human mitochondrial DNA maintenance and transcription.Frontiers in cell and developmental biology · 2022
    Review
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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 2 institutions in 1 country.

Robert F GahlLaboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda 20892, MD, USA.
Pallavi DwivediLaboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda 20892, MD, USA.
Nico TjandraLaboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda 20892, MD, USA.
National Heart Lung and Blood Institute · USNational Institutes of Health · US

Funding

Regulation of mitochondria morphologyZIAHL006064 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI TJANDRA, NICO · 2010 to 2025
$20.9M
6 · The paper itself

Abstract

The most critical step in the initiation of apoptosis is the activation of the Bcl-2 family of proteins to oligomerize and permeabilize the outer-mitochondrial membrane (OMM). As this step results in the irreversible release of factors that enhance cellular degradation, it is the point of no return in programmed cell death and would be an ideal therapeutic target. However, the arrangement of the Bcl-2 proteins in the OMM during permeabilization still remains unknown. It is also unclear whether the Bcl-2 protein, Bid, directly participates in the formation of the oligomers in live cells, even though it is cleaved and translocates to the OMM at the initiation of apoptosis. Therefore, we utilized confocal microscopy to measure Förster resonance energy transfer (FRET) efficiencies in live cells to determine the conformation(s) and intermolecular contacts of Bid within these Bcl-2 oligomers. We found that Bid adopts an extended conformation, which appears to be critical for its association with the mitochondrial membrane. This conformation is also important for intermolecular contacts within the Bid oligomer. More importantly for the first time, direct intermolecular contacts between Bid and Bax were observed, thereby, confirming Bid as a key component of these oligomers. Furthermore, the observed FRET efficiencies allowed us to propose an oligomeric arrangement of Bid, Bax, and possibly other members of the Bcl-2 family of proteins that form a self-propagating network that permeabilizes the OMM.

Indexed as

ApoptosisAnimalsbcl-2-Associated X ProteinBH3 Interacting Domain Death Agonist ProteinCross-Linking ReagentsFluorescence Resonance Energy TransferMiceMitochondriaMitochondrial MembranesModels, BiologicalPermeabilityProtein ConformationProtein Transportbcl-2-Associated X ProteinBH3 Interacting Domain Death Agonist ProteinCross-Linking Reagents

Identifiers

PMID27763642
PMCPMC5133987
OpenAlexW2538905465

What OpenQuestion holds

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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.