Evidence map›Paper›PMID 25476776›Full record

ArticleCell death and differentiation2015

CHCHD2 inhibits apoptosis by interacting with Bcl-x L to regulate Bax activation.

Y Liu, H V Clegg, P L Leslie, J Di, L A Tollini, Y He, T-H Kim, A Jin, L M Graves, J Zheng and 1 more

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

Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

66 citing papers in PubMed, 113 citations in OpenAlex.

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  15. Involvement of Mitochondria in Parkinson's Disease.International journal of molecular sciences · 2023
    Review
  16. Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2023
    Article
  17. Clinical chorioamnionitis at term is characterized by changes in the plasma concentration of CHCHD2/MNRR1, a mitochondrial protein.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2023
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6 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

11 authors at 2 institutions in 2 countries.

Y Liu1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [3] Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China.
H V Clegg1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [3] Curriculum in Genetics and Molecular Biology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
P L Leslie1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [3] Curriculum in Genetics and Molecular Biology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
J Di1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [3] Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China.
L A Tollini1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [3] Curriculum in Genetics and Molecular Biology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Y He1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [3] Curriculum in Genetics and Molecular Biology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
T-H Kim1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
A Jin1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
L M GravesDepartment of Pharmacology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
J ZhengLaboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China.
Y Zhang1] Department of Radiation Oncology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [3] Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China [4] Department of Pharmacology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
University of North Carolina at Chapel Hill · USXuzhou Medical College · CN

Funding

NRSA IN GENETICST32GM007092 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEKELSKY, JEFF J. · 1985 to 2019
$5.9M
CANCER CELL BIOLOGY TRAINING PROGRAMT32CA071341 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHANNING J. DER, Yuliya Pylayeva-Gupta · 1996 to 2026
$5.0M
Regulation of MDM2 by the ribosomal protein L11R01CA100302 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZHANG, YANPING · 2003 to 2013
$3.2M
Mitochondrial p32 regulation of the Mdm2-p53 tumor suppression signaling and apopR01CA155235 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZHANG, YANPING · 2012 to 2016
$1.5M
The in vivo role of the Mdm2-MdmX interaction in p53 regulationR01CA167637 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZHANG, YANPING · 2012 to 2016
$1.5M
In vivo function of Mdm2 E3 ubiquitin ligaseR01CA127770 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZHANG, YANPING · 2008 to 2013
$1.5M
NCI NIH HHS 5T32CA071341NCI NIH HHS CA100302NCI NIH HHS CA127770NCI NIH HHS CA155235NCI NIH HHS CA167637NCI NIH HHS R01 CA100302NCI NIH HHS R01 CA127770NCI NIH HHS R01 CA155235NCI NIH HHS R01 CA167637NCI NIH HHS T32 CA071341NIGMS NIH HHS T32 GM007092
6 · The paper itself

Abstract

Mitochondrial outer membrane permeabilization (MOMP) is a critical control point during apoptosis that results in the release of pro-apoptotic mitochondrial contents such as cytochrome c. MOMP is largely controlled by Bcl-2 family proteins such as Bax, which under various apoptotic stresses becomes activated and oligomerizes on the outer mitochondrial membrane. Bax oligomerization helps promote the diffusion of the mitochondrial contents into the cytoplasm activating the caspase cascade. In turn, Bax is regulated primarily by anti-apoptotic Bcl-2 proteins including Bcl-xL, which was recently shown to prevent Bax from accumulating at the mitochondria. However, the exact mechanisms by which Bcl-xL regulates Bax and thereby MOMP remain partially understood. In this study, we show that the small CHCH-domain-containing protein CHCHD2 binds to Bcl-xL and inhibits the mitochondrial accumulation and oligomerization of Bax. Our data show that in response to apoptotic stimuli, mitochondrial CHCHD2 decreases prior to MOMP. Furthermore, when CHCHD2 is absent from the mitochondria, the ability of Bcl-xL to inhibit Bax activation and to prevent apoptosis is attenuated, which results in increases in Bax oligomerization, MOMP and apoptosis. Collectively, our findings establish CHCHD2, a previously uncharacterized small mitochondrial protein with no known homology to the Bcl-2 family, as one of the negative regulators of mitochondria-mediated apoptosis.

Indexed as

Apoptosisbcl-2-Associated X Proteinbcl-X ProteinBlotting, WesternCell Line, TumorCell SurvivalDNA-Binding ProteinsHeLa CellsHumansImmunoprecipitationMitochondriaMitochondrial MembranesMitochondrial ProteinsProtein BindingTranscription Factorsbcl-2-Associated X Proteinbcl-X ProteinCHCHD2 protein, humanDNA-Binding ProteinsMitochondrial ProteinsTranscription Factors

Identifiers

PMID25476776
PMCPMC4423185
OpenAlexW2093518043

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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.