Evidence map›Paper›PMID 25482509›Full record

ArticleMolecular cell2015

Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis.

Thibaud T Renault, Konstantinos V Floros, Rana Elkholi, Kelly-Ann Corrigan, Yulia Kushnareva, Shira Y Wieder, Claudia Lindtner, Madhavika N Serasinghe, James J Asciolla, Christoph Buettner and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed
8.5field-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

114 citing papers in PubMed, 215 citations in OpenAlex.

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  17. The bioenergetic landscape of cancer.Molecular metabolism · 2024
    Review
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54 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 1 country.

Thibaud T RenaultDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Konstantinos V FlorosDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Rana ElkholiDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Kelly-Ann CorriganDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Yulia KushnarevaDivision of Immune Regulation, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Shira Y WiederDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Claudia LindtnerDepartment of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Madhavika N SerasingheDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
James J AsciollaDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Christoph BuettnerThe Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Donald D NewmeyerDivision of Immune Regulation, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Jerry E ChipukDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: jerry.chipuk@mssm.edu.
Icahn School of Medicine at Mount Sinai · USLa Jolla Institute for Immunology · US

Funding

Project 2P20AA017067 · NIAAA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FRIEDMAN, SCOTT L. · 2008 to 2012
$2.5M
A Role of Hypothalamic Dysfunction in Alcoholic Liver DiseaseR01AA023416 · NIAAA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BUETTNER, CHRISTOPH · 2014 to 2018
$2.2M
Function and regulation of the BCL-2 familyR01CA157740 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHIPUK, JERRY EDWARD · 2011 to 2015
$1.7M
The role of Stat3 signaling in leptin's pleitropic action.K08DK074873 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BUETTNER, CHRISTOPH · 2006 to 2009
$510k
The role of the endocannabinoid system in regulating hepatic glucose fluxesR03DK082724 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BUETTNER, CHRISTOPH · 2009 to 2010
$169k
NCI NIH HHS CA157740NCI NIH HHS R01 CA157740NIAAA NIH HHS NIH P20AA017067NIAAA NIH HHS P20 AA017067NIAAA NIH HHS R01 AA023416NIDDK NIH HHS DK082724NIDDK NIH HHS DK083568NIDDK NIH HHS K08 DK074873NIDDK NIH HHS R03 DK082724
6 · The paper itself

Abstract

Proapoptotic BCL-2 proteins converge upon the outer mitochondrial membrane (OMM) to promote mitochondrial outer membrane permeabilization (MOMP) and apoptosis. Here we investigated the mechanistic relationship between mitochondrial shape and MOMP and provide evidence that BAX requires a distinct mitochondrial size to induce MOMP. We utilized the terminal unfolded protein response pathway to systematically define proapoptotic BCL-2 protein composition after stress and then directly interrogated their requirement for a productive mitochondrial size. Complementary biochemical, cellular, in vivo, and ex vivo studies reveal that Mfn1, a GTPase involved in mitochondrial fusion, establishes a mitochondrial size that is permissive for proapoptotic BCL-2 family function. Cells with hyperfragmented mitochondria, along with size-restricted OMM model systems, fail to support BAX-dependent membrane association and permeabilization due to an inability to stabilize BAXα9·membrane interactions. This work identifies a mechanistic contribution of mitochondrial size in dictating BAX activation, MOMP, and apoptosis.

Indexed as

AnimalsApoptosisApoptosis Regulatory Proteinsbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinBcl-2-Like Protein 11Gene Expression RegulationGTP PhosphohydrolasesMembrane Potential, MitochondrialMembrane ProteinsMiceMitochondrial DynamicsMitochondria, LiverMitochondrial MembranesOrganelle ShapePermeabilityApoptosis Regulatory ProteinsBak1 protein, mouseBax protein, mousebcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinBcl2l11 protein, mouseBcl-2-Like Protein 11GTP PhosphohydrolasesMembrane ProteinsMfn1 protein, mouseProto-Oncogene ProteinsUnilamellar Liposomes

Identifiers

PMID25482509
PMCPMC4289414
OpenAlexW2049807952

What OpenQuestion holds

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Registered trials

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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.