Evidence map›Paper›PMID 37903764›Full record

ArticleNature communications2023

DIAPH1-MFN2 interaction regulates mitochondria-SR/ER contact and modulates ischemic/hypoxic stress.

Gautham Yepuri, Lisa M Ramirez, Gregory G Theophall, Sergei V Reverdatto, Nosirudeen Quadri, Syed Nurul Hasan, Lei Bu, Devi Thiagarajan, Robin Wilson, Raquel López Díez and 11 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
6.9field-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

36 citing papers in PubMed, 45 citations in OpenAlex.

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  18. Activation of Lysosomal Retrograde Transport Triggers TPC1-IP3R1 CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    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

21 authors at 3 institutions in 1 country.

Gautham YepuriDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.
Lisa M RamirezDepartment of Chemistry, University of Albany, State University of New York, Albany, NY, 12222, USA.ORCID 0000-0002-4072-325X
Gregory G TheophallDepartment of Chemistry, University of Albany, State University of New York, Albany, NY, 12222, USA.
Sergei V ReverdattoDepartment of Chemistry, University of Albany, State University of New York, Albany, NY, 12222, USA.
Nosirudeen QuadriDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.
Syed Nurul HasanDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.
Lei BuDepartment of Medicine, Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Devi ThiagarajanDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.
Robin WilsonDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.
Raquel López DíezDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.ORCID 0000-0003-4468-4654
Paul F GuggerDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.
Kaamashri MangarDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.
Navneet NarulaDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Stuart D KatzDepartment of Medicine, Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Boyan ZhouDepartment of Population Health, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Huilin LiDepartment of Population Health, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Aleksandr B StotlandDepartment of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Roberta A GottliebDepartment of Biomedical Sciences, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.ORCID 0000-0002-1432-006X
Ann Marie SchmidtDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA.ORCID 0000-0001-8902-070X
Alexander ShekhtmanDepartment of Chemistry, University of Albany, State University of New York, Albany, NY, 12222, USA.ORCID 0000-0003-2649-2675
Ravichandran RamasamyDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, New York, 10016, USA. ravichandran.ramasamy@nyulangone.org.ORCID 0000-0001-9502-8265
New York University · USAlbany State University · USCedars-Sinai Medical Center · US

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Richard Lewis Possemato · 1985 to 2026
$83.1M
Project 3: RAGE/DIAPH1 interactions and cellular stressP01HL146367 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SCHMIDT, ANN MARIE · 2019 to 2023
$12.5M
Targeting RAGE-mDia1 in Diabetic Complications: Mechanisms and TherapeuticsR24DK103032 · NIDDK · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI RAMASAMY, RAVICHANDRAN, SCHMIDT, ANN MARIE · 2014 to 2018
$4.2M
Targeting RAGE/DIAPH1: Novel Therapeutic Strategy for Diabetic ComplicationsR01DK122456 · NIDDK · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI RAMASAMY, RAVICHANDRAN, SCHMIDT, ANN MARIE · 2020 to 2024
$3.1M
Real Time (RT) In-cell NMR technology to study protein interactions in live cellsR01GM085006 · NIGMS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI SHEKHTMAN, ALEXANDER · 2010 to 2021
$2.4M
NCI NIH HHS P30 CA016087NHLBI NIH HHS P01 HL146367NIDDK NIH HHS R01 DK122456NIDDK NIH HHS R24 DK103032NIGMS NIH HHS R01 GM085006
6 · The paper itself

Abstract

Inter-organelle contact and communication between mitochondria and sarco/endoplasmic reticulum (SR/ER) maintain cellular homeostasis and are profoundly disturbed during tissue ischemia. We tested the hypothesis that the formin Diaphanous-1 (DIAPH1), which regulates actin dynamics, signal transduction and metabolic functions, contributes to these processes. We demonstrate that DIAPH1 interacts directly with Mitofusin-2 (MFN2) to shorten mitochondria-SR/ER distance, thereby enhancing mitochondria-ER contact in cells including cardiomyocytes, endothelial cells and macrophages. Solution structure studies affirm the interaction between the Diaphanous Inhibitory Domain and the cytosolic GTPase domain of MFN2. In male rodent and human cardiomyocytes, DIAPH1-MFN2 interaction regulates mitochondrial turnover, mitophagy, and oxidative stress. Introduction of synthetic linker construct, which shorten the mitochondria-SR/ER distance, mitigated the molecular and functional benefits of DIAPH1 silencing in ischemia. This work establishes fundamental roles for DIAPH1-MFN2 interaction in the regulation of mitochondria-SR/ER contact networks. We propose that targeting pathways that regulate DIAPH1-MFN2 interactions may facilitate recovery from tissue ischemia.

Indexed as

Endothelial CellsMitochondriaAnimalsEndoplasmic ReticulumForminsGTP PhosphohydrolasesHumansIschemiaMaleMitochondrial ProteinsSignal TransductionDIAPH1 protein, humanForminsGTP PhosphohydrolasesMFN2 protein, humanMitochondrial Proteins

Identifiers

PMID37903764
PMCPMC10616211
OpenAlexW4388033354

What OpenQuestion holds

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LicenceCC BY
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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.