Evidence map›Paper›PMID 25419710›Full record

ArticleNature medicine2014

Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity.

Ana Paula Arruda, Benedicte M Pers, Güneş Parlakgül, Ekin Güney, Karen Inouye, Gökhan S Hotamisligil

Abstract readVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 383 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
383citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

383 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024
    Pooled it
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  18. CabioRxiv : the preprint server for biology · 2026
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323 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

6 authors.

Ana Paula ArrudaDepartment of Genetics and Complex Diseases and Sabri Ülker Center, Harvard School of Public Health and Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.
Benedicte M PersDepartment of Genetics and Complex Diseases and Sabri Ülker Center, Harvard School of Public Health and Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.
Güneş ParlakgülDepartment of Genetics and Complex Diseases and Sabri Ülker Center, Harvard School of Public Health and Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.ORCID 0000000193657287
Ekin GüneyDepartment of Genetics and Complex Diseases and Sabri Ülker Center, Harvard School of Public Health and Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.
Karen InouyeDepartment of Genetics and Complex Diseases and Sabri Ülker Center, Harvard School of Public Health and Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.
Gökhan S HotamisligilDepartment of Genetics and Complex Diseases and Sabri Ülker Center, Harvard School of Public Health and Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.

Funding

TNF RECEPTOR FUNCTION IN INSULIN RESISTANCE AND OBESITYR01DK052539 · NIDDK · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HOTAMISLIGIL, GOKHAN S · 1998 to 2017
$6.8M
Deconvolution of adaptive metabolic responses of the endoplasmic reticulumRC4DK090942 · NIDDK · HARVARD SCHOOL OF PUBLIC HEALTH · PI HOTAMISLIGIL, GOKHAN S · 2010 to 2010
$2.4M
NIDDK NIH HHS 1RC4-DK090942NIDDK NIH HHS DK52539NIDDK NIH HHS R01 DK052539NIDDK NIH HHS RC4 DK090942
6 · The paper itself

Abstract

Proper function of the endoplasmic reticulum (ER) and mitochondria is crucial for cellular homeostasis, and dysfunction at either site has been linked to pathophysiological states, including metabolic diseases. Although the ER and mitochondria play distinct cellular roles, these organelles also form physical interactions with each other at sites defined as mitochondria-associated ER membranes (MAMs), which are essential for calcium, lipid and metabolite exchange. Here we show that in the liver, obesity leads to a marked reorganization of MAMs resulting in mitochondrial calcium overload, compromised mitochondrial oxidative capacity and augmented oxidative stress. Experimental induction of ER-mitochondria interactions results in oxidative stress and impaired metabolic homeostasis, whereas downregulation of PACS-2 or IP3R1, proteins important for ER-mitochondria tethering or calcium transport, respectively, improves mitochondrial oxidative capacity and glucose metabolism in obese animals. These findings establish excessive ER-mitochondrial coupling as an essential component of organelle dysfunction in obesity that may contribute to the development of metabolic pathologies such as insulin resistance and diabetes.

Indexed as

AnimalsCalciumCalnexinDisease Models, AnimalDown-RegulationEndoplasmic ReticulumEndoplasmic Reticulum StressGlucoseGTP PhosphohydrolasesHepatocytesInositol 1,4,5-Trisphosphate ReceptorsLipid MetabolismLiverMiceMicroscopy, Electron, TransmissionMitochondriaCalciumCalnexinGlucoseGTP PhosphohydrolasesInositol 1,4,5-Trisphosphate ReceptorsIp3r2 protein, mouseItpr1 protein, mouseMfn2 protein, mousePacs2 protein, mouseVesicular Transport Proteins

Identifiers

PMID25419710
PMCPMC4412031

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.