Evidence mapPaperPMID 41310646Full record

ArticleCell communication and signaling : CCS2025

Mitochondrial connexin 43 modulates metabolic stress adaptation in glioma cell lines.

Anna Gervasi, Simona Denaro, Simona D'Aprile, Maja Potokar, Jernej Jorgačevski, Robert Zorec, Daniele Tibullo, Agata Zappalà, Angela Maria Amorini, Rosalba Parenti and 1 more

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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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

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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

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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. Article
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4 · The record

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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.

Anna GervasiSection of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, 95123, Italy.
Simona DenaroSection of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, 95123, Italy.
Simona D'AprileSection of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, 95123, Italy.
Maja PotokarLaboratory of Neuroendocrinology‑Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia.
Jernej JorgačevskiLaboratory of Neuroendocrinology‑Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia.
Robert ZorecLaboratory of Neuroendocrinology‑Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia.
Daniele TibulloSection of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, 95123, Italy.
Agata ZappalàSection of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, 95123, Italy.
Angela Maria AmoriniSection of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, 95123, Italy.
Rosalba ParentiSection of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, 95123, Italy. parenti@unict.it.
Nunzio VicarioSection of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, 95123, Italy. nunzio.vicario@unict.it.

Funding

National Biodiversity Future Center (NBFC) by the European Union NextGenerationEU, PNRR; META-CONNECT- Spoke 6 CN00000033National Plan for NRRP Complementary Investments (PNC, established with the decree-law 6 May 2021, n. 59, converted by law n. 101 of 2021) in the call for the funding of research initiatives for technologies and innovative trajectories in the health and care sectors (Directorial Decree n. 931 of 06-06-2022)-AdvaNced Technologies for Human-centrEd Medicine - ANTHEM PNC0000003
6 · The paper itself

Abstract

backgroundConnexin 43 (CX43) is a hemichannel (HC)- and gap junction (GJ)-forming protein that mediates the exchange of small molecules between the intracellular and extracellular environments, as well as intercellular communication. In addition to this canonical role, recent studies have shown that its functions range from transcriptional regulation to intracellular homeostasis. The ability of CX43 to translocate into mitochondria suggests its involvement in energy metabolism. However, the functions of mitochondrial CX43 (mt-CX43) in neural cells remain unexplored.

methodsOur study investigated the expression and localisation of mt-CX43 through western blot and immunofluorescence analyses in four immortalised human glioma cell lines: T98-G, A-172, CCF-STTG1, and U-87 MG. Additionally, targeted metabolomic analysis was conducted to assess changes in key metabolic pathways.

resultsBasal CX43 expression and extracellular stress factors, particularly cell density and extracellular pH fluctuations, significantly modulated the mitochondrial localisation of CX43. Inhibition of the heat shock protein 90 (HSP90) chaperone system by geldanamycin (GA) resulted in a marked reduction in mt-CX43, suggesting an import mechanism involving HSP90 and the translocase of the outer membrane (TOM) complex. In addition, the assessment of key metabolites revealed increased purine biosynthesis in T98-G cells exposed to GA treatment, characterised by lower basal CX43 expression and reduced mt-CX43 levels under stress conditions. Conversely, U-87 MG cells exhibited a stable NAD

conclusionsOur results suggest that mt-CX43 serves as a multifunctional regulator of metabolic adaptation and stress response in glioma cell lines. Our results extend the role of mt-CX43 as an essential factor in cellular metabolic plasticity, providing new insights into the modulation of metabolic imbalances and mitochondrial dysfunction.

Indexed as

Adaptation, PhysiologicalConnexin 43GliomaMitochondriaStress, PhysiologicalCell Line, TumorHSP90 Heat-Shock ProteinsHumansConnexin 43HSP90 Heat-Shock ProteinsCX43GeldanamycinGlioblastomaMetabolismpHPurine

Identifiers

PMID41310646
PMCPMC12659480

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.