Cell recovery by reversal of ferroptosis
The classical view of cell death has long assumed that, once initiated, the dying process is irreversible. However, recent studies reveal that recovery of dying cells can actually occur, even after initiation of a cell suicide process called apoptosis. This discovery raised fundamental key questions...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2019-06-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/8/6/bio043182 |
| _version_ | 1831684328079228928 |
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| author | Ho Man Tang Ho Lam Tang |
| author_facet | Ho Man Tang Ho Lam Tang |
| author_sort | Ho Man Tang |
| collection | DOAJ |
| description | The classical view of cell death has long assumed that, once initiated, the dying process is irreversible. However, recent studies reveal that recovery of dying cells can actually occur, even after initiation of a cell suicide process called apoptosis. This discovery raised fundamental key questions about which forms of the cell death process could be reversible and how reversal is mediated. Here, we uncover an unanticipated reversibility of ferroptotic cell death process. Unlike apoptosis reversal, removal of ferroptosis inducers, such as erastin and glutamate, is insufficient to allow ferroptotic dying cells to escape the cell death process. However, by removing the cell death inducer and providing the reduced form of glutathione or the radical-trapping antioxidant ferrostatin-1, ferroptotic dying cells can be rescued and promoted to recover. Interestingly, although ferroptotic inhibitors such as aminooxyacetic acid, deferoxamine, dopamine and vitamin C can prevent initiation of ferroptosis, added alone they are unable to reverse the initiated ferroptosis, suggesting regulatory distinctions between preventing and reversing ferroptosis. Together, these results reveal the first evidence that ferroptosis is reversible and suggest strategies to enhance its reversibility, thereby providing a useful model for studying the physiological, pathological and therapeutic potentials of this cell recovery process. |
| first_indexed | 2024-12-20T06:54:50Z |
| format | Article |
| id | doaj.art-9a081c5e94024367be7bb8700e459bea |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-20T06:54:50Z |
| publishDate | 2019-06-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-9a081c5e94024367be7bb8700e459bea2022-12-21T19:49:24ZengThe Company of BiologistsBiology Open2046-63902019-06-018610.1242/bio.043182043182Cell recovery by reversal of ferroptosisHo Man Tang0Ho Lam Tang1 Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA The classical view of cell death has long assumed that, once initiated, the dying process is irreversible. However, recent studies reveal that recovery of dying cells can actually occur, even after initiation of a cell suicide process called apoptosis. This discovery raised fundamental key questions about which forms of the cell death process could be reversible and how reversal is mediated. Here, we uncover an unanticipated reversibility of ferroptotic cell death process. Unlike apoptosis reversal, removal of ferroptosis inducers, such as erastin and glutamate, is insufficient to allow ferroptotic dying cells to escape the cell death process. However, by removing the cell death inducer and providing the reduced form of glutathione or the radical-trapping antioxidant ferrostatin-1, ferroptotic dying cells can be rescued and promoted to recover. Interestingly, although ferroptotic inhibitors such as aminooxyacetic acid, deferoxamine, dopamine and vitamin C can prevent initiation of ferroptosis, added alone they are unable to reverse the initiated ferroptosis, suggesting regulatory distinctions between preventing and reversing ferroptosis. Together, these results reveal the first evidence that ferroptosis is reversible and suggest strategies to enhance its reversibility, thereby providing a useful model for studying the physiological, pathological and therapeutic potentials of this cell recovery process.http://bio.biologists.org/content/8/6/bio043182AnastasisFerrostatin-1GlutamateGlutathioneReversal of apoptosisReversal of ferroptosis |
| spellingShingle | Ho Man Tang Ho Lam Tang Cell recovery by reversal of ferroptosis Biology Open Anastasis Ferrostatin-1 Glutamate Glutathione Reversal of apoptosis Reversal of ferroptosis |
| title | Cell recovery by reversal of ferroptosis |
| title_full | Cell recovery by reversal of ferroptosis |
| title_fullStr | Cell recovery by reversal of ferroptosis |
| title_full_unstemmed | Cell recovery by reversal of ferroptosis |
| title_short | Cell recovery by reversal of ferroptosis |
| title_sort | cell recovery by reversal of ferroptosis |
| topic | Anastasis Ferrostatin-1 Glutamate Glutathione Reversal of apoptosis Reversal of ferroptosis |
| url | http://bio.biologists.org/content/8/6/bio043182 |
| work_keys_str_mv | AT homantang cellrecoverybyreversalofferroptosis AT holamtang cellrecoverybyreversalofferroptosis |