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https://www.arca.fiocruz.br/handle/icict/62279
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ArtigoDireito Autoral
Acesso restrito
Data de embargo
3100-12-31
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Mostrar registro completo
GASDERMIN D PERMEABILIZATION OF MITOCHONDRIAL INNER AND OUTER MEMBRANES ACCELERATES AND ENHANCES PYROPTOSIS
Autor(es)
Miao, Rui
Jiang, Cong
Chang, Winston Y.
Zhang, Haiwei
An, Jinsu
Ho, Felicia
Chen, Pengcheng
Zhang, Han
Junqueira, Caroline Furtado
Amgalan, Dulguun
Liang, Felix G.
Zhang, Junbing
Evavold, Charles L.
Hafner-Bratkovič, Iva
Zhang, Zhibin
Fontana, Pietro
Xia, Shiyu
Waldeck-Weiermair, Markus
Pan, Youdong
Michel, Thomas
Bar-Peled, Liron
Wu, Hao
Kagan, Jonathan C.
Kitsis, Richard N.
Zhang, Peng
Liu, Xing
Lieberman, Judy
Jiang, Cong
Chang, Winston Y.
Zhang, Haiwei
An, Jinsu
Ho, Felicia
Chen, Pengcheng
Zhang, Han
Junqueira, Caroline Furtado
Amgalan, Dulguun
Liang, Felix G.
Zhang, Junbing
Evavold, Charles L.
Hafner-Bratkovič, Iva
Zhang, Zhibin
Fontana, Pietro
Xia, Shiyu
Waldeck-Weiermair, Markus
Pan, Youdong
Michel, Thomas
Bar-Peled, Liron
Wu, Hao
Kagan, Jonathan C.
Kitsis, Richard N.
Zhang, Peng
Liu, Xing
Lieberman, Judy
Afiliação
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
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
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Key Laboratory of RNA Science and Engineering. Shanghai Institute of Immunity and Infection. Chinese Academy of Sciences. Shanghai, China
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
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, Brazil
Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA
Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA
Center for Cancer Research. Massachusetts General Hospital and Department of Medicine. Harvard Medical School. Boston, MA, USA
Ragon Institute of Mass General, MIT and Harvard. Cambridge, MA, USA
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
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
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
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
Brigham and Women’s Hospital. Department of Medicine. Cardiovascular Division. Harvard Medical School. Boston, MA, USA
Department of Dermatology and Harvard Skin Disease Research Center. Brigham and Women’s Hospital, Harvard Medical School. Boston, MA, USA
Brigham and Women’s Hospital. Department of Medicine. Cardiovascular Division. Harvard Medical School. Boston, MA, USA
Center for Cancer Research. Massachusetts General Hospital and Department of Medicine. Harvard Medical School. Boston, MA, USA
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
Division of Gastroenterology. Boston Children’s Hospital and Harvard Medical School. Boston, MA, USA
Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA
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
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
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
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Key Laboratory of RNA Science and Engineering. Shanghai Institute of Immunity and Infection. Chinese Academy of Sciences. Shanghai, China
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
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, Brazil
Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA
Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA
Center for Cancer Research. Massachusetts General Hospital and Department of Medicine. Harvard Medical School. Boston, MA, USA
Ragon Institute of Mass General, MIT and Harvard. Cambridge, MA, USA
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
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
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
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
Brigham and Women’s Hospital. Department of Medicine. Cardiovascular Division. Harvard Medical School. Boston, MA, USA
Department of Dermatology and Harvard Skin Disease Research Center. Brigham and Women’s Hospital, Harvard Medical School. Boston, MA, USA
Brigham and Women’s Hospital. Department of Medicine. Cardiovascular Division. Harvard Medical School. Boston, MA, USA
Center for Cancer Research. Massachusetts General Hospital and Department of Medicine. Harvard Medical School. Boston, MA, USA
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
Division of Gastroenterology. Boston Children’s Hospital and Harvard Medical School. Boston, MA, USA
Departments of Medicine and Cell Biology. Wilf Family Cardiovascular Research Institute. Albert Einstein College of Medicine. Bronx, New York, NY, USA
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
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Resumo em Inglês
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.
Editor
Elsevier
Referência
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.e8, 2023. https://doi.org/10.1016/j.immuni.2023.10.004ISSN
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