| Author | Miao, Rui | |
| Author | Jiang, Cong | |
| Author | Chang, Winston Y. | |
| Author | Zhang, Haiwei | |
| Author | An, Jinsu | |
| Author | Ho, Felicia | |
| Author | Chen, Pengcheng | |
| Author | Zhang, Han | |
| Author | Junqueira, Caroline Furtado | |
| Author | Amgalan, Dulguun | |
| Author | Liang, Felix G. | |
| Author | Zhang, Junbing | |
| Author | Evavold, Charles L. | |
| Author | Hafner-Bratkovič, Iva | |
| Author | Zhang, Zhibin | |
| Author | Fontana, Pietro | |
| Author | Xia, Shiyu | |
| Author | Waldeck-Weiermair, Markus | |
| Author | Pan, Youdong | |
| Author | Michel, Thomas | |
| Author | Bar-Peled, Liron | |
| Author | Wu, Hao | |
| Author | Kagan, Jonathan C. | |
| Author | Kitsis, Richard N. | |
| Author | Zhang, Peng | |
| Author | Liu, Xing | |
| Author | Lieberman, Judy | |
| Access date | 2024-01-18T12:30:31Z | |
| Available date | 2024-01-18T12:30:31Z | |
| Document date | 2023 | |
| Citation | MIAO, Rui et al. Gasdermin D permeabilization of mitochondrial inner and outer membranes accelerates and enhances pyroptosis. Immunity, v. 56, n. 11, p. 2523-2541, Nov. 2023. | en_US |
| ISSN | 1074-7613 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/62279 | |
| Language | eng | en_US |
| Publisher | Cell Press | en_US |
| Previous version | https://www.arca.fiocruz.br/handle/icict/67662 | |
| Rights | open access | en_US |
| Title | Gasdermin D permeabilization of mitochondrial inner and outer membranes accelerates and enhances pyroptosis | en_US |
| Type | Article | en_US |
| DOI | 10.1016/j.immuni.2023.10.004 | |
| Abstract | Gasdermin D (GSDMD)-activated inflammatory cell death (pyroptosis) causes mitochondrial damage, but its underlying mechanism and functional consequences are largely unknown. Here, we show that the N-terminal pore-forming GSDMD fragment (GSDMD-NT) rapidly damaged both inner and outer mitochondrial membranes (OMMs) leading to reduced mitochondrial numbers, mitophagy, ROS, loss of transmembrane potential, attenuated oxidative phosphorylation (OXPHOS), and release of mitochondrial proteins and DNA from the matrix and intermembrane space. Mitochondrial damage occurred as soon as GSDMD was cleaved prior to plasma membrane damage. Mitochondrial damage was independent of the B-cell lymphoma 2 family and depended on GSDMD-NT binding to cardiolipin. Canonical and noncanonical inflammasome activation of mitochondrial damage, pyroptosis, and inflammatory cytokine release were suppressed by genetic ablation of cardiolipin synthase (Crls1) or the scramblase (Plscr3) that transfers cardiolipin to the OMM. Phospholipid scramblase-3 (PLSCR3) deficiency in a tumor compromised pyroptosis-triggered anti-tumor immunity. Thus, mitochondrial damage plays a critical role in pyroptosis. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Pediatrics. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Department of Thoracic Surgery. Shanghai Pulmonary Hospital. School of Medicine. Tongji University. Shanghai, China / Key Laboratory of RNA Science and Engineering. Shanghai Institute of Immunity and Infection. Chinese Academy of Sciences. Shanghai, China. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Pediatrics. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Pediatrics. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Pediatrics. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Pediatrics. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Key Laboratory of RNA Science and Engineering. Shanghai Institute of Immunity and Infection. Chinese Academy of Sciences. Shanghai, China. | en_US |
| Affilliation | Department of Thoracic Surgery. Shanghai Pulmonary Hospital. School of Medicine. Tongji University. Shanghai, China / Key Laboratory of RNA Science and Engineering. Shanghai Institute of Immunity and Infection. Chinese Academy of Sciences. Shanghai, China. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Pediatrics. Harvard Medical School. Boston, MA, USA / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA. | en_US |
| Affilliation | Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA. | en_US |
| Affilliation | Center for Cancer Research. Massachusetts General Hospital and Department of Medicine. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Ragon Institute of Mass General. MIT and Harvard. Cambridge, MA, USA. | en_US |
| Affilliation | Division of Gastroenterology. Boston Children’s Hospital and Harvard Medical School. Boston, MA, USA / Department of Synthetic Biology and Immunology. National Institute of Chemistry and EN-FIST Centre of Excellence and Faculty of Medicine. University of Ljubljana. Ljubljana, Slovenia. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Pediatrics. Harvard Medical School. Boston, MA, USA / Department of Immunology. The University of Texas MD Anderson Cancer Center. Houston, TX, USA. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Biological Chemistry and Molecular Pharmacology. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Biological Chemistry and Molecular Pharmacology. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Brigham and Women’s Hospital. Department of Medicine. Cardiovascular Division. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Department of Dermatology and Harvard Skin Disease Research Center. Brigham and Women’s Hospital. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Brigham and Women’s Hospital. Department of Medicine. Cardiovascular Division. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Center for Cancer Research. Massachusetts General Hospital and Department of Medicine. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Biological Chemistry and Molecular Pharmacology. Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Division of Gastroenterology. Boston Children’s Hospital and Harvard Medical School. Boston, MA, USA. | en_US |
| Affilliation | Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA. | en_US |
| Affilliation | Department of Thoracic Surgery. Shanghai Pulmonary Hospital. School of Medicine. Tongji University. Shanghai, China. | en_US |
| Affilliation | Key Laboratory of RNA Science and Engineering. Shanghai Institute of Immunity and Infection. Chinese Academy of Sciences. Shanghai, China. | en_US |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA / Department of Pediatrics. Harvard Medical School. Boston, MA, USA. | en_US |
| Subject | CRLS1 | en_US |
| Subject | GSDMD | en_US |
| Subject | IL-1 | en_US |
| Subject | PLSCR3 | en_US |
| Subject | Cardiolipin | en_US |
| Subject | Mitochondria | en_US |
| Subject | Pyroptosis | en_US |
| e-ISSN | 1097-4180 | |
