Energy metabolism rewiring following acute UVB irradiation is largely dependent on nuclear DNA damage
Solar ultraviolet B (UVB) radiation-induced DNA damage is a well-known initiator of skin carcinomas. The UVB-induced DNA damage response (DDR) involves series of signaling cascades that are activated to maintain cell integrity. Among the different biological processes, little is known about the role of energy metabolism in the DDR. We sought to determine whether UVB-induced nuclear and/or mitochondrial cyclobutane pyrimidine dimers (CPDs) alter cellular energy metabolism. To gain insight into this question, we took advantage of keratinocytes expressing nuclear or mitochondrial CPD photolyase. Applying a quantitative proteomic approach and targeted metabolomics, we observed biphasic alterations in multiple metabolic pathways and in the abundance of various metabolites, largely influenced by the presence of genomic CPDs. The heightened oxygen consumption rate post-irradiation, along with mitochondrial structural rearrangements, was found to be dependent on both mitochondrial and nuclear CPDs. Understanding the influence of nuclear and mitochondrial DNA damage on keratinocyte responses to UVB irradiation deepens current knowledge regarding skin cancer prevention, initiation, and therapy.
Authors
- Muriel Cario (ORCID: https://orcid.org/0000-0003-0462-5684)
- Hala Fatrouni (ORCID: https://orcid.org/0009-0002-2925-914X)
- Anni I. Nieminen (ORCID: https://orcid.org/0000-0001-8999-6040)
- Laure Favot-Laforge
- Elodie Muzotte (ORCID: https://orcid.org/0000-0002-1721-940X)
- Walid Mahfouf
- Seppo Vainio (ORCID: https://orcid.org/0000-0001-9319-3566)
- Stéphane Claverol (ORCID: https://orcid.org/0000-0001-5315-2823)
- Hamid Rezvani (ORCID: https://orcid.org/0000-0001-8067-1338)
- François Moisan (ORCID: https://orcid.org/0000-0003-2680-7497)
- Nsrein Ali (ORCID: https://orcid.org/0000-0001-9173-3717)
- Rodrigue Rossignol (ORCID: https://orcid.org/0000-0002-8983-2465)
- Corinne Faucheux (ORCID: https://orcid.org/0000-0001-7842-3204)
- L. Dousset (ORCID: https://orcid.org/0000-0002-5332-5736)
- Hadi Younes
- Ferial Khalife
Institutions
- Université de Bordeaux (FR)
- Inserm (FR)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Université de Poitiers (FR)
- Bordeaux Population Health (FR)
- Information Management Services (US)
- Hôpital Saint-André (FR)
- Institute for Molecular Medicine Finland (FI)
- Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers (FR)
- Centre de Recherche Cardio-Thoracique de Bordeaux (FR)
- Institut de Génomique Fonctionnelle (FR)
- Maladies Rares: Génétique et Métabolisme (FR)
- BoRdeaux Institute of onCology (FR)
- University of Oulu (FI)
Publication Details
- Journal
- Free Radical Biology and Medicine
- Published
- 2024-12-10
- DOI
- https://doi.org/10.1016/j.freeradbiomed.2024.12.030
- Citations
- 4
- Primary Topic
- Skin Protection and Aging
- Type
- article
- Field-Weighted Citation Impact
- 2.14
Funders
- Institut National Du Cancer