Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells
Myoferlin, an emerging oncoprotein, has been associated with a low survival in several cancer types including pancreas ductal adenocarcinoma where it controls mitochondria structure and respiratory functions. Owing to the high susceptibility of KRAS-mutated cancer cells to iron-dependent cell death,...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722000969 |
| _version_ | 1811257075245776896 |
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| author | Gilles Rademaker Yasmine Boumahd Raphaël Peiffer Sandy Anania Tom Wissocq Maude Liégeois Géraldine Luis Nor Eddine Sounni Ferman Agirman Naïma Maloujahmoum Pascal De Tullio Marc Thiry Akeila Bellahcène Vincent Castronovo Olivier Peulen |
| author_facet | Gilles Rademaker Yasmine Boumahd Raphaël Peiffer Sandy Anania Tom Wissocq Maude Liégeois Géraldine Luis Nor Eddine Sounni Ferman Agirman Naïma Maloujahmoum Pascal De Tullio Marc Thiry Akeila Bellahcène Vincent Castronovo Olivier Peulen |
| author_sort | Gilles Rademaker |
| collection | DOAJ |
| description | Myoferlin, an emerging oncoprotein, has been associated with a low survival in several cancer types including pancreas ductal adenocarcinoma where it controls mitochondria structure and respiratory functions. Owing to the high susceptibility of KRAS-mutated cancer cells to iron-dependent cell death, ferroptosis, and to the high iron content in mitochondria, we investigated the relation existing between mitochondrial integrity and iron-dependent cell death. We discovered that myoferlin targeting with WJ460 pharmacological compound triggered mitophagy and ROS accumulation culminating with lipid peroxidation and apoptosis-independent cell death. WJ460 caused a reduction of the abundance of ferroptosis core regulators xc- cystine/glutamate transporter and GPX-4. Mitophagy inhibitor Mdivi1 and iron chelators inhibited the myoferlin-related ROS production and restored cell growth. Additionally, we reported a synergic effect between ferroptosis inducers, erastin and RSL3, and WJ460. |
| first_indexed | 2024-04-12T17:51:04Z |
| format | Article |
| id | doaj.art-825b81d9bde840298a5b3b5ded7cf2a2 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-12T17:51:04Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-825b81d9bde840298a5b3b5ded7cf2a22022-12-22T03:22:30ZengElsevierRedox Biology2213-23172022-07-0153102324Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cellsGilles Rademaker0Yasmine Boumahd1Raphaël Peiffer2Sandy Anania3Tom Wissocq4Maude Liégeois5Géraldine Luis6Nor Eddine Sounni7Ferman Agirman8Naïma Maloujahmoum9Pascal De Tullio10Marc Thiry11Akeila Bellahcène12Vincent Castronovo13Olivier Peulen14Metastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, Belgium; Center for Interdisciplinary Research on Medicines (CIRM), Mitochondria Adaptation in Cancer Group, University of Liège, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, Belgium; Center for Interdisciplinary Research on Medicines (CIRM), Mitochondria Adaptation in Cancer Group, University of Liège, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, Belgium; Center for Interdisciplinary Research on Medicines (CIRM), Mitochondria Adaptation in Cancer Group, University of Liège, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, BelgiumLaboratory of Cellular and Molecular Immunology, GIGA Institute, University of Liège, B-4000, Liège, BelgiumLaboratory of Tumor and Development Biology, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, BelgiumLaboratory of Tumor and Development Biology, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, BelgiumCenter for Interdisciplinary Research on Medicines (CIRM), Metabolomics Group, University of Liège, B-4000, Liège, BelgiumLaboratory of Cellular and Tissular Biology, GIGA-Neurosciences, Cell Biology L3, University of Liège, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, BelgiumMetastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, Belgium; Center for Interdisciplinary Research on Medicines (CIRM), Mitochondria Adaptation in Cancer Group, University of Liège, B-4000, Liège, Belgium; Corresponding author. Metastasis Research Laboratory, GIGA-cancer, University of Liège, Pathology Institute B23, B-4000, Liège, Belgium.Myoferlin, an emerging oncoprotein, has been associated with a low survival in several cancer types including pancreas ductal adenocarcinoma where it controls mitochondria structure and respiratory functions. Owing to the high susceptibility of KRAS-mutated cancer cells to iron-dependent cell death, ferroptosis, and to the high iron content in mitochondria, we investigated the relation existing between mitochondrial integrity and iron-dependent cell death. We discovered that myoferlin targeting with WJ460 pharmacological compound triggered mitophagy and ROS accumulation culminating with lipid peroxidation and apoptosis-independent cell death. WJ460 caused a reduction of the abundance of ferroptosis core regulators xc- cystine/glutamate transporter and GPX-4. Mitophagy inhibitor Mdivi1 and iron chelators inhibited the myoferlin-related ROS production and restored cell growth. Additionally, we reported a synergic effect between ferroptosis inducers, erastin and RSL3, and WJ460.http://www.sciencedirect.com/science/article/pii/S2213231722000969MyoferlinFerroptosisMitochondriaPancreas cancerMitophagy |
| spellingShingle | Gilles Rademaker Yasmine Boumahd Raphaël Peiffer Sandy Anania Tom Wissocq Maude Liégeois Géraldine Luis Nor Eddine Sounni Ferman Agirman Naïma Maloujahmoum Pascal De Tullio Marc Thiry Akeila Bellahcène Vincent Castronovo Olivier Peulen Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells Redox Biology Myoferlin Ferroptosis Mitochondria Pancreas cancer Mitophagy |
| title | Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells |
| title_full | Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells |
| title_fullStr | Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells |
| title_full_unstemmed | Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells |
| title_short | Myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells |
| title_sort | myoferlin targeting triggers mitophagy and primes ferroptosis in pancreatic cancer cells |
| topic | Myoferlin Ferroptosis Mitochondria Pancreas cancer Mitophagy |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722000969 |
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