Golgi stress mediates redox imbalance and ferroptosis in human cells.
| Title: | Golgi stress mediates redox imbalance and ferroptosis in human cells. |
|---|---|
| Authors: | Alborzinia H; BioMed X Innovation Center, Im Neuenheimer Feld 583, 69120 Heidelberg, Germany.; 4Present Address: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.; Ignashkova TI; BioMed X Innovation Center, Im Neuenheimer Feld 583, 69120 Heidelberg, Germany.; Dejure FR; BioMed X Innovation Center, Im Neuenheimer Feld 583, 69120 Heidelberg, Germany.; Gendarme M; BioMed X Innovation Center, Im Neuenheimer Feld 583, 69120 Heidelberg, Germany.; Theobald J; 2Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.; Wölfl S; 2Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.; Lindemann RK; 3Translational Innovation Platform Oncology, Merck Biopharma, Merck KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany.; Reiling JH; BioMed X Innovation Center, Im Neuenheimer Feld 583, 69120 Heidelberg, Germany.; 5Present Address: Institute for Applied Cancer Science and Center for Co-Clinical Trials, University of Texas MD Anderson Cancer Center, Houston, TX USA. |
| Source: | Communications biology [Commun Biol] 2018 Nov 28; Vol. 1, pp. 210. Date of Electronic Publication: 2018 Nov 28 (Print Publication: 2018). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: eCollection Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]- |
| Abstract: | Cytotoxic activities of several Golgi-dispersing compounds including AMF-26/M-COPA, brefeldin A and golgicide A have previously been shown to induce autophagy or apoptosis. Here, we demonstrate that these Golgi disruptors also trigger ferroptosis, a non-apoptotic form of cell death characterized by iron-dependent oxidative degradation of lipids. Inhibitors of ferroptosis not only counteract cell death, but they also protect from Golgi dispersal and inhibition of protein secretion in response to several Golgi stress agents. Furthermore, the application of sublethal doses of ferroptosis-inducers such as erastin and sorafenib, low cystine growth conditions, or genetic knockdown of SLC7A11 and GPX4 all similarly protect cells from Golgi stress and lead to modulation of ACSL4, SLC7A5, SLC7A11 or GPX4 levels. Collectively, this study suggests a previously unrecognized function of the Golgi apparatus, which involves cellular redox control and prevents ferroptotic cell death. |
| Competing Interests: | The authors declare no competing interests. |
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| Entry Date(s): | Date Created: 20181205 Latest Revision: 20200304 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC6262011 |
| DOI: | 10.1038/s42003-018-0212-6 |
| PMID: | 30511023 |
| Database: | MEDLINE |
Journal Article