Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities
The mitochondrial chaperone TRAP1 exerts protective functions under diverse stress conditions. It induces metabolic rewiring and safeguards cancer cells from oxidative insults, thereby contributing to neoplastic progression.TRAP1 works as a homodimer, but recent evidence indicated that it forms tetr...
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Elsevier
2025-07-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725001909 |
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| author | Fiorella Faienza Claudio Laquatra Matteo Castelli Gianmarco Matrullo Salvatore Rizza Federica Guarra Azam Roshani Dashtmian Alessia Magro Paola Giglio Chiara Pecorari Lavinia Ferrone Elisabetta Moroni Francesca Pacello Andrea Battistoni Giorgio Colombo Andrea Rasola Giuseppe Filomeni |
| author_facet | Fiorella Faienza Claudio Laquatra Matteo Castelli Gianmarco Matrullo Salvatore Rizza Federica Guarra Azam Roshani Dashtmian Alessia Magro Paola Giglio Chiara Pecorari Lavinia Ferrone Elisabetta Moroni Francesca Pacello Andrea Battistoni Giorgio Colombo Andrea Rasola Giuseppe Filomeni |
| author_sort | Fiorella Faienza |
| collection | DOAJ |
| description | The mitochondrial chaperone TRAP1 exerts protective functions under diverse stress conditions. It induces metabolic rewiring and safeguards cancer cells from oxidative insults, thereby contributing to neoplastic progression.TRAP1 works as a homodimer, but recent evidence indicated that it forms tetramers whose effects remain elusive. Here, we find that TRAP1 generates redox-sensitive tetramers via disulfide bonds involving cysteines 261 and 573. TRAP1 tetramerization is elicited by oxidative stress and abrogated upon expression of the double C261S/C573R mutant. In cancer cells, the TRAP1 C261S/C573R mutant is unable to inhibit the activity of its client succinate dehydrogenase and to confer protection against oxidative insults, thus hampering the invasiveness of aggressive sarcoma cells.Overall, our findings indicate that TRAP1 undergoes tetramerization in response to oxidative stress and identify C261 and C573 as critical for TRAP1 structural rearrangement and functions. |
| format | Article |
| id | doaj-art-971a14521ab2420cab8e3f0c199f80f4 |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-971a14521ab2420cab8e3f0c199f80f42025-08-20T01:57:12ZengElsevierRedox Biology2213-23172025-07-018410367710.1016/j.redox.2025.103677Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activitiesFiorella Faienza0Claudio Laquatra1Matteo Castelli2Gianmarco Matrullo3Salvatore Rizza4Federica Guarra5Azam Roshani Dashtmian6Alessia Magro7Paola Giglio8Chiara Pecorari9Lavinia Ferrone10Elisabetta Moroni11Francesca Pacello12Andrea Battistoni13Giorgio Colombo14Andrea Rasola15Giuseppe Filomeni16Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, I-00133, Rome, ItalyDepartment of Biomedical Sciences, University of Padova, viale G. Colombo 3, I-35131, Padova, ItalyDepartment of Chemistry, University of Pavia, via Taramelli 12, Pavia, I-27100, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, I-00133, Rome, Italy; Redox Biology, Danish Cancer Institute, Strandboulevarden 49, DK-2100, Copenhagen, DenmarkRedox Biology, Danish Cancer Institute, Strandboulevarden 49, DK-2100, Copenhagen, DenmarkDepartment of Chemistry, University of Pavia, via Taramelli 12, Pavia, I-27100, ItalyDepartment of Biomedical Sciences, University of Padova, viale G. Colombo 3, I-35131, Padova, ItalyDepartment of Biomedical Sciences, University of Padova, viale G. Colombo 3, I-35131, Padova, ItalyRedox Biology, Danish Cancer Institute, Strandboulevarden 49, DK-2100, Copenhagen, DenmarkRedox Biology, Danish Cancer Institute, Strandboulevarden 49, DK-2100, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Padova, viale G. Colombo 3, I-35131, Padova, ItalySCITEC-CNR, via Mario Bianco 9, I-20131, Milano, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, I-00133, Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, I-00133, Rome, ItalyDepartment of Chemistry, University of Pavia, via Taramelli 12, Pavia, I-27100, ItalyDepartment of Biomedical Sciences, University of Padova, viale G. Colombo 3, I-35131, Padova, Italy; Corresponding author.Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, I-00133, Rome, Italy; Redox Biology, Danish Cancer Institute, Strandboulevarden 49, DK-2100, Copenhagen, Denmark; Corresponding author. Redox Biology, Danish Cancer Institute, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.The mitochondrial chaperone TRAP1 exerts protective functions under diverse stress conditions. It induces metabolic rewiring and safeguards cancer cells from oxidative insults, thereby contributing to neoplastic progression.TRAP1 works as a homodimer, but recent evidence indicated that it forms tetramers whose effects remain elusive. Here, we find that TRAP1 generates redox-sensitive tetramers via disulfide bonds involving cysteines 261 and 573. TRAP1 tetramerization is elicited by oxidative stress and abrogated upon expression of the double C261S/C573R mutant. In cancer cells, the TRAP1 C261S/C573R mutant is unable to inhibit the activity of its client succinate dehydrogenase and to confer protection against oxidative insults, thus hampering the invasiveness of aggressive sarcoma cells.Overall, our findings indicate that TRAP1 undergoes tetramerization in response to oxidative stress and identify C261 and C573 as critical for TRAP1 structural rearrangement and functions.http://www.sciencedirect.com/science/article/pii/S2213231725001909Oxidative stressMitochondriaCysteineTumorigenesisMetabolism |
| spellingShingle | Fiorella Faienza Claudio Laquatra Matteo Castelli Gianmarco Matrullo Salvatore Rizza Federica Guarra Azam Roshani Dashtmian Alessia Magro Paola Giglio Chiara Pecorari Lavinia Ferrone Elisabetta Moroni Francesca Pacello Andrea Battistoni Giorgio Colombo Andrea Rasola Giuseppe Filomeni Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities Redox Biology Oxidative stress Mitochondria Cysteine Tumorigenesis Metabolism |
| title | Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities |
| title_full | Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities |
| title_fullStr | Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities |
| title_full_unstemmed | Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities |
| title_short | Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities |
| title_sort | disulfide mediated tetramerization of trap1 fosters its antioxidant and pro neoplastic activities |
| topic | Oxidative stress Mitochondria Cysteine Tumorigenesis Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725001909 |
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