Energy metabolism rewiring following acute UVB irradiation is largely dependent on nuclear DNA damage
Dousset, Léa; Mahfouf, Walid; Younes, Hadi; Fatrouni, Hala; Faucheux, Corinne; Muzotte, Elodie; Khalife, Ferial; Rossignol, Rodrigue; Moisan, François; Cario, Muriel; Claverol, Stéphane; Favot-Laforge, Laure; Nieminen, Anni I; Vainio, Seppo; Ali, Nsrein; Rezvani, Hamid-Reza (2024-12-10)
Elsevier
10.12.2024
Léa Dousset, Walid Mahfouf, Hadi Younes, Hala Fatrouni, Corinne Faucheux, Elodie Muzotte, Ferial Khalife, Rodrigue Rossignol, François Moisan, Muriel Cario, Stéphane Claverol, Laure Favot-Laforge, Anni I. Nieminen, Seppo Vainio, Nsrein Ali, Hamid-Reza Rezvani, Energy metabolism rewiring following acute UVB irradiation is largely dependent on nuclear DNA damage, Free Radical Biology and Medicine, Volume 227, 2025, Pages 459-471, ISSN 0891-5849, https://doi.org/10.1016/j.freeradbiomed.2024.12.030
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202412167294
https://urn.fi/URN:NBN:fi:oulu-202412167294
Tiivistelmä
Abstract
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.
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.
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