Conformational Switch Driven Membrane Pore Formation byMycobacteriumSecretory Protein MPT63 Induces Macrophage Cell Death

2019 ◽  
Vol 14 (7) ◽  
pp. 1601-1610 ◽  
Author(s):  
Achinta Sannigrahi ◽  
Indrani Nandi ◽  
Sayantani Chall ◽  
Junaid Jibran Jawed ◽  
Animesh Halder ◽  
...  
Keyword(s):  
Cell Death ◽  
Pore Formation ◽  
Macrophage Cell ◽  
Conformational Switch ◽  
Membrane Pore

scholarly journals Bacterial gasdermins reveal an ancient mechanism of cell death

Science ◽  
2022 ◽  
Vol 375 (6577) ◽  
pp. 221-225
Author(s):  
Alex G. Johnson ◽  
Tanita Wein ◽  
Megan L. Mayer ◽  
Brianna Duncan-Lowey ◽  
Erez Yirmiya ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Cell Death ◽  
Pore Formation ◽  
Central Component ◽  
Defense System ◽  
Inhibitory Peptide ◽  
Proteolytic Activation ◽  
Membrane Pore ◽  
Membrane Pores ◽  
Bacteriophage Infection

Ancient origin of cell death Gasdermins are cell death proteins in mammals that form membrane pores in response to pathogen infection. Johnson et al . report that diverse bacteria encode structural and functional homologs of mammalian gasdermins. Like their mammalian counterparts, bacterial gasdermins are activated by caspase-like proteases, oligomerize into large membrane pores, and defend against pathogen—in this case, bacteriophage—infection. Proteolytic activation occurs through the release of a short inhibitory peptide, and many bacterial gasdermins are lipidated to facilitate membrane pore formation. Pyroptotic cell death, a central component of mammalian innate immunity, thus has a shared origin with an ancient antibacteriophage defense system. —SMH

scholarly journals GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death

2016 ◽  
Vol 35 (16) ◽  
pp. 1766-1778 ◽  
Author(s):  
Lorenzo Sborgi ◽  
Sebastian Rühl ◽  
Estefania Mulvihill ◽  
Joka Pipercevic ◽  
Rosalie Heilig ◽  
...  
Keyword(s):  
Cell Death ◽  
Pore Formation ◽  
Membrane Pore

Membrane pore formation at protein–lipid interfaces

2014 ◽  
Vol 39 (11) ◽  
pp. 510-516 ◽  
Author(s):  
Robert J.C. Gilbert ◽  
Mauro Dalla Serra ◽  
Christopher J. Froelich ◽  
Mark I. Wallace ◽  
Gregor Anderluh
Keyword(s):  
Pore Formation ◽  
Membrane Pore

scholarly journals Molecular Basis for Membrane Pore Formation by Bax Protein Carboxyl Terminus

Biochemistry ◽  
2012 ◽  
Vol 51 (46) ◽  
pp. 9406-9419 ◽  
Author(s):  
Suren A. Tatulian ◽  
Pranav Garg ◽  
Kathleen N. Nemec ◽  
Bo Chen ◽  
Annette R. Khaled
Keyword(s):  
Molecular Basis ◽  
Pore Formation ◽  
Carboxyl Terminus ◽  
Membrane Pore ◽  
Bax Protein

scholarly journals Plasma-borne indicators of inflammasome activity in Parkinson’s disease patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Faith L. Anderson ◽  
Katharine M. von Herrmann ◽  
Angeline S. Andrew ◽  
Yuliya I. Kuras ◽  
Alison L. Young ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Inflammasome Activation ◽  
Membrane Pore ◽  
Related Proteins ◽  
Inflammasome Activity

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss but no diagnosis of PD identified elevated expression of inflammasome-related proteins and activation-related “speck” formation in degenerating mesencephalic tissues compared with controls. Based on previous reports of circulating inflammasome proteins in patients suffering from heritable syndromes caused by hyper-activation of the NLRP3 inflammasome, we evaluated PD patient plasma for evidence of inflammasome activity. Multiple circulating inflammasome proteins were detected almost exclusively in extracellular vesicles indicative of ongoing inflammasome activation and pyroptosis. Analysis of plasma obtained from a multi-center cohort identified elevated plasma-borne NLRP3 associated with PD status. Our findings are consistent with others indicating inflammasome activity in neurodegenerative disorders. Findings suggest mesencephalic inflammasome protein expression as a histopathologic marker of early-stage nigral degeneration and suggest plasma-borne inflammasome-related proteins as a potentially useful class of biomarkers for patient stratification and the detection and monitoring of inflammation in PD.

scholarly journals Targeting macrophage necroptosis for therapeutic and diagnostic interventions in atherosclerosis

2016 ◽  
Vol 2 (7) ◽  
pp. e1600224 ◽  
Author(s):  
Denuja Karunakaran ◽  
Michele Geoffrion ◽  
Lihui Wei ◽  
Wei Gan ◽  
Laura Richards ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Plaque Rupture ◽  
Ex Vivo ◽  
Density Lipoprotein ◽  
Necrotic Core ◽  
Atherosclerotic Plaques ◽  
Core Formation ◽  
Macrophage Cell ◽  
Plaque Instability

Atherosclerosis results from maladaptive inflammation driven primarily by macrophages, whose recruitment and proliferation drive plaque progression. In advanced plaques, macrophage death contributes centrally to the formation of plaque necrosis, which underlies the instability that promotes plaque rupture and myocardial infarction. Hence, targeting macrophage cell death pathways may offer promise for the stabilization of vulnerable plaques. Necroptosis is a recently discovered pathway of programmed cell necrosis regulated by RIP3 and MLKL kinases that, in contrast to apoptosis, induces a proinflammatory state. We show herein that necroptotic cell death is activated in human advanced atherosclerotic plaques and can be targeted in experimental atherosclerosis for both therapeutic and diagnostic interventions. In humans with unstable carotid atherosclerosis, expression of RIP3 and MLKL is increased, and MLKL phosphorylation, a key step in the commitment to necroptosis, is detected in advanced atheromas. Investigation of the molecular mechanisms underlying necroptosis showed that atherogenic forms of low-density lipoprotein increase RIP3 and MLKL transcription and phosphorylation—two critical steps in the execution of necroptosis. Using a radiotracer developed with the necroptosis inhibitor necrostatin-1 (Nec-1), we show that 123I-Nec-1 localizes specifically to atherosclerotic plaques in Apoe−/− mice, and its uptake is tightly correlated to lesion areas by ex vivo nuclear imaging. Furthermore, treatment of Apoe−/− mice with established atherosclerosis with Nec-1 reduced lesion size and markers of plaque instability, including necrotic core formation. Collectively, our findings offer molecular insight into the mechanisms of macrophage cell death that drive necrotic core formation in atherosclerosis and suggest that this pathway can be used as both a diagnostic and therapeutic tool for the treatment of unstable atherosclerosis.

scholarly journals Calcineurin Orchestrates Lateral Transfer ofAspergillus fumigatusduring Macrophage Cell Death

2016 ◽  
Vol 194 (9) ◽  
pp. 1127-1139 ◽  
Author(s):  
Anand Shah ◽  
Shichina Kannambath ◽  
Susanne Herbst ◽  
Andrew Rogers ◽  
Simona Soresi ◽  
...  
Keyword(s):  
Cell Death ◽  
Lateral Transfer ◽  
Macrophage Cell

Mechanisms of Membrane Pore Formation by Amyloidogenic Peptides in Amyotrophic Lateral Sclerosis

2016 ◽  
Vol 22 (29) ◽  
pp. 9958-9961 ◽  
Author(s):  
Charles H. Chen ◽  
Ayesha Khan ◽  
Joseph Jen-Tse Huang ◽  
Martin B. Ulmschneider
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Pore Formation ◽  
Membrane Pore ◽  
Amyloidogenic Peptides ◽  
Lateral Sclerosis
Sign in / Sign up

Export Citation Format

Share Document