Mitochondrial chaperonin DNAJC15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cells
DNAJC15 is a mitochondrial TIMM23-related co-chaperonin known for its role in regulating oxidative phosphorylation efficiency, oxidative stress response and lipid metabolism. Recently, it has been proposed that the loss of DNAJC15 correlates with cisplatin (CDDP)-resistance onset in ovarian cancer (...
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| Language: | English |
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The Royal Society
2025-01-01
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.240151 |
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| author | Stefano Miglietta Manuela Sollazzo Iacopo Gherardi Sara Milioni Beatrice Cavina Lorena Marchio Monica De Luise Camelia Alexandra Coada Marco Fiorillo Anna Myriam Perrone Ivana Kurelac Giuseppe Gasparre Luisa Iommarini Anna Maria Ghelli Anna Maria Porcelli |
| author_facet | Stefano Miglietta Manuela Sollazzo Iacopo Gherardi Sara Milioni Beatrice Cavina Lorena Marchio Monica De Luise Camelia Alexandra Coada Marco Fiorillo Anna Myriam Perrone Ivana Kurelac Giuseppe Gasparre Luisa Iommarini Anna Maria Ghelli Anna Maria Porcelli |
| author_sort | Stefano Miglietta |
| collection | DOAJ |
| description | DNAJC15 is a mitochondrial TIMM23-related co-chaperonin known for its role in regulating oxidative phosphorylation efficiency, oxidative stress response and lipid metabolism. Recently, it has been proposed that the loss of DNAJC15 correlates with cisplatin (CDDP)-resistance onset in ovarian cancer (OC), suggesting this protein as a potential prognostic factor during OC progression. However, the molecular mechanisms through which DNAJC15 contributes to CDDP response remains poorly investigated. Here, we show that high levels of DNAJC15 are associated with accumulation of lipid droplets, decreased tumorigenic features and increased sensitivity to CDDP in OC cells. When overexpressed, DNAJC15 induced a phenotype displaying increased lipid peroxidation and subsequent ferroptosis induction. To prove a role for DNAJC15-induced ferroptosis in promoting sensitivity to CDDP, we reduced lipid peroxidation upon Ferrostatin 1 treatment, which decreased cells’ vulnerability to ferroptosis ultimately recovering their CDDP-resistant phenotype. In conclusion, our study uncovers the role of DNAJC15 in modulating ferroptosis activation and in the onset of CDDP resistance in OC cells. |
| format | Article |
| id | doaj-art-2b62dcd5d27349ac8dedddd4a1d00433 |
| institution | Kabale University |
| issn | 2046-2441 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj-art-2b62dcd5d27349ac8dedddd4a1d004332025-01-16T17:59:35ZengThe Royal SocietyOpen Biology2046-24412025-01-0115110.1098/rsob.240151Mitochondrial chaperonin DNAJC15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cellsStefano Miglietta0Manuela Sollazzo1Iacopo Gherardi2Sara Milioni3Beatrice Cavina4Lorena Marchio5Monica De Luise6Camelia Alexandra Coada7Marco Fiorillo8Anna Myriam Perrone9Ivana Kurelac10Giuseppe Gasparre11Luisa Iommarini12Anna Maria Ghelli13Anna Maria Porcelli14Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, ItalyCentre for Applied Biomedical Research (CRBA), University of Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, ItalyDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, ItalyCentre for Applied Biomedical Research (CRBA), University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDNAJC15 is a mitochondrial TIMM23-related co-chaperonin known for its role in regulating oxidative phosphorylation efficiency, oxidative stress response and lipid metabolism. Recently, it has been proposed that the loss of DNAJC15 correlates with cisplatin (CDDP)-resistance onset in ovarian cancer (OC), suggesting this protein as a potential prognostic factor during OC progression. However, the molecular mechanisms through which DNAJC15 contributes to CDDP response remains poorly investigated. Here, we show that high levels of DNAJC15 are associated with accumulation of lipid droplets, decreased tumorigenic features and increased sensitivity to CDDP in OC cells. When overexpressed, DNAJC15 induced a phenotype displaying increased lipid peroxidation and subsequent ferroptosis induction. To prove a role for DNAJC15-induced ferroptosis in promoting sensitivity to CDDP, we reduced lipid peroxidation upon Ferrostatin 1 treatment, which decreased cells’ vulnerability to ferroptosis ultimately recovering their CDDP-resistant phenotype. In conclusion, our study uncovers the role of DNAJC15 in modulating ferroptosis activation and in the onset of CDDP resistance in OC cells.https://royalsocietypublishing.org/doi/10.1098/rsob.240151DNAJC15ovarian cancercisplatin resistanceferroptosismitochondria |
| spellingShingle | Stefano Miglietta Manuela Sollazzo Iacopo Gherardi Sara Milioni Beatrice Cavina Lorena Marchio Monica De Luise Camelia Alexandra Coada Marco Fiorillo Anna Myriam Perrone Ivana Kurelac Giuseppe Gasparre Luisa Iommarini Anna Maria Ghelli Anna Maria Porcelli Mitochondrial chaperonin DNAJC15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cells Open Biology DNAJC15 ovarian cancer cisplatin resistance ferroptosis mitochondria |
| title | Mitochondrial chaperonin DNAJC15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cells |
| title_full | Mitochondrial chaperonin DNAJC15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cells |
| title_fullStr | Mitochondrial chaperonin DNAJC15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cells |
| title_full_unstemmed | Mitochondrial chaperonin DNAJC15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cells |
| title_short | Mitochondrial chaperonin DNAJC15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cells |
| title_sort | mitochondrial chaperonin dnajc15 promotes vulnerability to ferroptosis of chemoresistant ovarian cancer cells |
| topic | DNAJC15 ovarian cancer cisplatin resistance ferroptosis mitochondria |
| url | https://royalsocietypublishing.org/doi/10.1098/rsob.240151 |
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