Evidence map›Paper›PMID 41214844›Full record

ArticlePhysiological reports2025

Secreted mitochondrial aspartyl-tRNA synthetase (DARS2) regulates TNFα signaling.

Benjamin S Johnson, Alex Cornwell, Daniela Farkas, Ilknur Yurtsever, Jessica A Joseph, Arun Pradhan, Laszlo Farkas, James D Londino, Joseph S Bednash, Rama K Mallampalli

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Physiological reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Review
  2. Article
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

10 authors.

Benjamin S JohnsonDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.
Alex CornwellDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.ORCID 0009-0003-0105-8191
Daniela FarkasDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.
Ilknur YurtseverDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.
Jessica A JosephDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.
Arun PradhanDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.
Laszlo FarkasDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.
James D LondinoDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.
Joseph S BednashDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.ORCID 0000-0003-3576-4388
Rama K MallampalliDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, Ohio, USA.ORCID 0000-0002-5782-4495

Funding

Regulation of Cardiolin Byosynthesis in Epithelial InjuryP01HL114453 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2014 to 2023
$21.3M
TNF-alpha Control of a Surfactant Enzyme in Lung InjuryR01HL081784 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2006 to 2024
$5.4M
F box-Induced Acute Lung Injury and ParkinR01HL096376 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2010 to 2025
$5.1M
Sepsis-Associated Immune Suppression and F-box ProteinsR01HL097376 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2009 to 2025
$5.1M
Examining the role of TRMT1 and tRNA methylation in acute lung injury and ARDSR01HL169586 · NHLBI · OHIO STATE UNIVERSITY · PI James David Londino · 2023 to 2026
$2.2M
Transfer RNAs as novel mediators in acute lung injuryK08HL169725 · NHLBI · OHIO STATE UNIVERSITY · PI Joseph Stanley Bednash · 2024 to 2026
$491k
HHS | National Institutes of Health (NIH) P01HL114453HHS | National Institutes of Health (NIH) R01HL081784HHS | National Institutes of Health (NIH) R01HL096376HHS | National Institutes of Health (NIH) R01HL097376NHLBI NIH HHS K08 HL169725NHLBI NIH HHS R01 HL169586
6 · The paper itself

Abstract

Aminoacyl-tRNA Synthetases (aaRS) are important regulators of cytokine signaling. Multiple cytoplasmic aaRS family members have been observed to be secreted in response to various stimuli to modulate downstream responses, however, agonist-induced cellular release of aaRS from mitochondria has not been described. In particular, TNFα is a potent mediator of aaRS release. BEAS-2B cells were utilized to study the release of mitochondrial Aspartyl-tRNA Synthetase (DARS2) in response to various cytokines. The role of DARS2 in paracrine signaling was evaluated using adoptive media transfer from BEAS-2B to recipient THP1 cells. To identify pathways governing DARS2 secretion, blocking antibodies chemical inhibitors and siRNA technology was employed. Herein, we describe DARS2 as the first mitochondrial aaRS released in response to TNFα from airway epithelia. Once secreted, DARS2 binds to macrophages, is internalized, thereby inducing an M1-like phenotype in recipient macrophages. DARS2 release from airway epithelia is in part, TNFα-receptor 1 dependent, and requires the endosomal sorting complex required for extracellular transport.

Indexed as

Aspartate-tRNA LigaseEpithelial CellsMitochondriaTumor Necrosis Factor-alphaCell LineCytokinesHumansMacrophagesParacrine CommunicationReceptors, Tumor Necrosis Factor, Type ITHP-1 CellsAspartate-tRNA LigaseCytokinesDARS2 protein, humanReceptors, Tumor Necrosis Factor, Type ITNFRSF1A protein, humanTumor Necrosis Factor-alphacytokineDARS2lung epitheliamitochondria

Identifiers

PMID41214844
PMCPMC12602254

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.