Stress Signaling and Cell Fate Determination: The Role of Mitochondria

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 30 September 2026 | Viewed by 786

Special Issue Editors


E-Mail Website
Guest Editor
UK Dementia Research Institute, University of Cambridge Island Research Building, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK
Interests: cell biology; organelle interactions; neurodegenerative disease

E-Mail Website
Guest Editor
Biomedical Science, School of Human Sciences, University of Derby, Derby DE22 1GB, UK
Interests: neurodegenerative disease; neurodevelopmental disease; ageing; autophagy

Special Issue Information

Dear Colleagues,

Mitochondria, far beyond their role as cellular powerhouses, are pivotal integrators and transducers of signals that critically determine cellular fate. These dynamic organelles orchestrate a complex interplay of signaling pathways, profoundly influencing cellular homeostasis, stress adaptation, and the critical decision points that lead to cell death. Mitochondrial signaling encompasses diverse mechanisms, such as inter-organelle communication (e.g., with the endoplasmic reticulum and nucleus), the release of crucial molecules like reactive oxygen species (ROS), calcium, and mitochondrial DNA (mtDNA), and the activation of integrated stress responses and retrograde signaling pathways that communicate mitochondrial status to the rest of the cell.

This Special Issue aims to thoroughly explore the intricate contributions of mitochondria to cellular demise mechanisms and associated stress responses, highlighting how these responses dictate cell survival or elimination. We invite original research articles, comprehensive reviews, and insightful mini-reviews that delve into the molecular mechanisms by which mitochondrial signals initiate, propagate, or regulate cell fate decisions under various stress conditions. Topics of interest include, but are not limited to, mitochondrial-nuclear retrograde signaling, mitochondrial dynamics, and mitochondrial quality control (e.g., mitophagy) as determinants of cell fate in response to stress, as well as the activation of integrated stress responses by mitochondrial dysfunction, leading to cell survival or programmed cell death. By consolidating cutting-edge research, this issue seeks to advance our understanding of mitochondrial signaling in cellular fate determination and highlight potential avenues for therapeutic intervention in diseases characterized by aberrant cell death.

Dr. Daniel Maddison
Dr. Bilal Malik
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mitochondria
  • cell death
  • integrated stress response
  • retrograde signaling
  • apoptosis
  • necroptosis
  • ferroptosis
  • mitophagy
  • mitochondrial dynamics
  • ROS
  • calcium signaling
  • inter-organelle communication

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:

Research

26 pages, 5299 KB  
Article
PeriTox-M, a Cell-Based Assay for Peripheral Neurotoxicity with Improved Sensitivity to Mitochondrial Inhibitors
by Anna-Katharina Holzer, Mira Dürr, Selina Multrus, Laura Dangel, Viktoria Magel and Marcel Leist
Cells 2025, 14(23), 1929; https://doi.org/10.3390/cells14231929 - 4 Dec 2025
Viewed by 547
Abstract
Human cell-based assays for neurotoxicity (NT) and developmental neurotoxicity (DNT) have reached a high level of readiness, but some tests require improvements in the specificity and sensitivity at which mitochondrial toxicants are detected. This study aimed to optimize the PeriTox assay, which uses [...] Read more.
Human cell-based assays for neurotoxicity (NT) and developmental neurotoxicity (DNT) have reached a high level of readiness, but some tests require improvements in the specificity and sensitivity at which mitochondrial toxicants are detected. This study aimed to optimize the PeriTox assay, which uses peripheral neurons (PNs) and predicts the potential of chemicals to trigger peripheral neuropathies. By introducing a glucose-to-galactose switch in the medium composition, cells were forced to rely on mitochondrial respiration. Using pre-differentiated PNs cultured in either glucose (Glc) or galactose (Gal), we observed no major differences in baseline phenotype, gene expression, neurite outgrowth, or total ATP content. However, a marked metabolic shift was confirmed by the increased oxygen consumption in Gal conditions. Based on measurements of neurite growth and ATP levels, Gal-adapted neurons showed a heightened sensitivity, up to 7500-fold, to a range of mitochondrial respiratory chain (MRC) inhibitors. The sensitivity shift was high for inhibitors of MRC complexes I and III and modest or absent for unrelated compounds such as proteasome inhibitors or cytoskeletal poisons. For complex I-III inhibitors, the enhanced detection of mitochondrial neurotoxicants was coupled with a more accurate distinction between cytotoxic and neurite-specific effects, i.e., an improved assay specificity. In conclusion, our study on 39 compounds suggests that running the PeriTox assay in galactose increases its sensitivity and specificity for several mitochondrial toxicants, while no general disadvantages or shortcomings were observed. The modified version (PeriTox-M) may increase the performance of in vitro test batteries for scientific and regulatory applications. Full article
Show Figures

Figure 1

Back to TopTop