Atovaquone-induced activation of the PERK/eIF2α signaling axis mitigates metabolic radiosensitisation
Our data highlight dual counter opposing impacts of atovaquone, serving as a hypoxic radiosensitiser though oxidative phosphorylation (OXPHOS) inhibition, but also in promoting stress induced ISR signaling, conferring resistance to radiation treatment. Importantly, if ISR activation is impeded, the metabolic radiosensitising properties of atovaquone is restored. These data provide a new insight to a molecular response that could help counteract hypoxia-induced radioresistance.
Authors
- Varun Pathak (ORCID: https://orcid.org/0000-0002-2655-4541)
- Reinhold J. Medina (ORCID: https://orcid.org/0000-0003-4351-7010)
- Niall M. Byrne (ORCID: https://orcid.org/0000-0002-3429-6685)
- Jonathan A. Coulter (ORCID: https://orcid.org/0000-0003-4112-2357)
- Tongchuan Wang
- Rayhanul Islam (ORCID: https://orcid.org/0000-0001-8621-2386)
- Jie Feng (ORCID: https://orcid.org/0000-0002-8261-6188)
- Sarah Chambers
Institutions
- University of Liverpool (GB)
Publication Details
- Journal
- Cell Communication and Signaling
- Published
- 2025-04-02
- DOI
- https://doi.org/10.1186/s12964-025-02160-9
- Citations
- 3
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 4.06
Funders
- Leverhulme Trust
- Dunhill Medical Trust
- Medical Research Council
- Engineering and Physical Sciences Research Council