Warnsmann 2018 Mech Ageing Dev: Difference between revisions
Beno Marija (talk | contribs) m (Beno Marija moved page Warnsmann 2017 Mech Ageing Dev to Warnsmann 2018 Mech Ageing Dev) |
Beno Marija (talk | contribs) No edit summary Β |
||
Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=Warnsmann V, Meyer N, Hamann A, KΓΆgel D, Osiewacz HD ( | |title=Warnsmann V, Meyer N, Hamann A, KΓΆgel D, Osiewacz HD (2018) A novel role of the mitochondrial permeability transition pore in (-)-gossypol-induced mitochondrial dysfunction. Mech Ageing Dev 170:45-58. | ||
|info=[https://www.ncbi.nlm.nih.gov/pubmed/28684269 PMID: 28684269] | |info=[https://www.ncbi.nlm.nih.gov/pubmed/28684269 PMID: 28684269] | ||
|authors=Warnsmann V, Meyer N, Hamann A, Koegel D, Osiewacz HD | |authors=Warnsmann V, Meyer N, Hamann A, Koegel D, Osiewacz HD | ||
|year= | |year=2018 | ||
|journal=Mech Ageing Dev | |journal=Mech Ageing Dev | ||
|abstract=Gossypol, a natural polyphenolic compound from cotton seeds, is known to trigger different forms of cell death in various types of cancer. Gossypol acts as a Bcl-2 inhibitor that induces apoptosis in apoptosis-competent cells. In apoptosis-resistant cancers such as glioblastoma, it triggers a non-apoptotic type of cell death associated with increased oxidative stress, mitochondrial depolarisation and fragmentation. In order to investigate the impact of gossypol on mitochondrial function, the mitochondrial permeability transition pore and on oxidative stress in more detail, we used the aging model ''Podospora anserina'' that lacks endogenous Bcl-2 proteins. We found that treatment with gossypol selectively increases hydrogen peroxide levels and impairs mitochondrial respiration in ''P. anserina'', apoptosis-deficient Bax/Bak double knockout mouse embryonal fibroblasts and glioblastoma cells. Significantly, we provide evidence that CYPD-mediated opening of the mPTP is required for gossypol-induced mitochondrial dysfunction, autophagy and cell death during organismic aging of ''P. anserina'' and in glioblastoma cells. Overall, these data provide new insights into the role of the mPTP and autophagy in the antitumor effects of gossypol, a natural compound that is clinically developed for the treatment of cancer. | |abstract=Gossypol, a natural polyphenolic compound from cotton seeds, is known to trigger different forms of cell death in various types of cancer. Gossypol acts as a Bcl-2 inhibitor that induces apoptosis in apoptosis-competent cells. In apoptosis-resistant cancers such as glioblastoma, it triggers a non-apoptotic type of cell death associated with increased oxidative stress, mitochondrial depolarisation and fragmentation. In order to investigate the impact of gossypol on mitochondrial function, the mitochondrial permeability transition pore and on oxidative stress in more detail, we used the aging model ''Podospora anserina'' that lacks endogenous Bcl-2 proteins. We found that treatment with gossypol selectively increases hydrogen peroxide levels and impairs mitochondrial respiration in ''P. anserina'', apoptosis-deficient Bax/Bak double knockout mouse embryonal fibroblasts and glioblastoma cells. Significantly, we provide evidence that CYPD-mediated opening of the mPTP is required for gossypol-induced mitochondrial dysfunction, autophagy and cell death during organismic aging of ''P. anserina'' and in glioblastoma cells. Overall, these data provide new insights into the role of the mPTP and autophagy in the antitumor effects of gossypol, a natural compound that is clinically developed for the treatment of cancer. | ||
|keywords=(β)-gossypol, Cell death, Mitochondrial dysfunction, Mitochondrial permeability transition pore, Oxidative stress | |keywords=(β)-gossypol, Cell death, Mitochondrial dysfunction, Mitochondrial permeability transition pore, Oxidative stress | ||
|editor=[[Kandolf G]], | |editor=[[Kandolf G]], | ||
Line 20: | Line 18: | ||
|pathways=N | |pathways=N | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=Labels, 2017-10 | |additional=Labels, 2017-10 | ||
}} | }} |
Latest revision as of 16:21, 23 March 2018
Warnsmann V, Meyer N, Hamann A, KΓΆgel D, Osiewacz HD (2018) A novel role of the mitochondrial permeability transition pore in (-)-gossypol-induced mitochondrial dysfunction. Mech Ageing Dev 170:45-58. |
Warnsmann V, Meyer N, Hamann A, Koegel D, Osiewacz HD (2018) Mech Ageing Dev
Abstract: Gossypol, a natural polyphenolic compound from cotton seeds, is known to trigger different forms of cell death in various types of cancer. Gossypol acts as a Bcl-2 inhibitor that induces apoptosis in apoptosis-competent cells. In apoptosis-resistant cancers such as glioblastoma, it triggers a non-apoptotic type of cell death associated with increased oxidative stress, mitochondrial depolarisation and fragmentation. In order to investigate the impact of gossypol on mitochondrial function, the mitochondrial permeability transition pore and on oxidative stress in more detail, we used the aging model Podospora anserina that lacks endogenous Bcl-2 proteins. We found that treatment with gossypol selectively increases hydrogen peroxide levels and impairs mitochondrial respiration in P. anserina, apoptosis-deficient Bax/Bak double knockout mouse embryonal fibroblasts and glioblastoma cells. Significantly, we provide evidence that CYPD-mediated opening of the mPTP is required for gossypol-induced mitochondrial dysfunction, autophagy and cell death during organismic aging of P. anserina and in glioblastoma cells. Overall, these data provide new insights into the role of the mPTP and autophagy in the antitumor effects of gossypol, a natural compound that is clinically developed for the treatment of cancer. β’ Keywords: (β)-gossypol, Cell death, Mitochondrial dysfunction, Mitochondrial permeability transition pore, Oxidative stress β’ Bioblast editor: Kandolf G β’ O2k-Network Lab: DE Frankfurt Osiewacz HD
Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology
Stress:Permeability transition Organism: Fungi
Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET
Pathway: N
HRR: Oxygraph-2k
Labels, 2017-10