Article
Multidisciplinary Sciences
Jargalsaikhan Dagvadorj, Karolina Mikulska-Ruminska, Gantsetseg Tumurkhuu, Rojo A. Ratsimandresy, Jessica Carriere, Allen M. Andres, Stefanie Marek-Iannucci, Yang Song, Shuang Chen, Malcolm Lane, Andrea Dorfleutner, Roberta A. Gottlieb, Christian Stehlik, Suzanne Cassel, Fayyaz S. Sutterwala, Ivet Bahar, Timothy R. Crother, Moshe Arditi
Summary: The balance between NLRP3 inflammasome activation and mitophagy is crucial for cellular homeostasis, with IL-1 alpha playing a key role in regulating this balance. IL-1 alpha deficiency can lead to altered cellular functions and health by affecting mitochondrial damage and NLRP3 inflammasome activation. The interaction between IL-1 alpha and mitochondrial cardiolipin disrupts mitophagy and enhances NLRP3 inflammasome activation, highlighting the importance of this regulatory mechanism in cellular health.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Yanbing Qiu, Yumei Huang, Meilin Chen, Yuqin Yang, Xiaoxu Li, Wenling Zhang
Summary: NLRP3 inflammasome is an intracellular polyprotein complex that is activated by perceiving different molecular patterns. Intracellular mtDNA and extracellular mtDNA have different functions in activating NLRP3 inflammasome.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiao Sun, Yingzhi Liu, Ziheng Huang, Wenye Xu, Wei Hu, Lina Yi, Zhe Liu, Hung Chan, Judeng Zeng, Xiaodong Liu, Huarong Chen, Jun Yu, Francis Ka Leung Chan, Siew Chien Ng, Sunny Hei Wong, Maggie Haitian Wang, Tony Gin, Gavin Matthew Joynt, David Shu Cheong Hui, Xuan Zou, Yuelong Shu, Christopher Hon Ki Cheng, Shisong Fang, Huanle Luo, Jing Lu, Matthew Tak Vai Chan, Lin Zhang, William Ka Kei Wu
Summary: A recent study found that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can activate the inflammasome and induce pyroptosis in lung epithelial cells, leading to severe COVID-19. NSP6 impairs lysosome acidification to inhibit autophagic flux and interacts with ATP6AP1 to inhibit its cleavage-mediated activation. A variant of NSP6 associated with asymptomatic COVID-19 exhibits reduced binding to ATP6AP1 and weakened ability to induce pyroptosis. This study suggests that pharmacological rectification of autophagic flux could be a potential therapeutic strategy for SARS-CoV-2 infection.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Immunology
Yingting Hou, Hongbin He, Ming Ma, Rongbin Zhou
Summary: NLRP3 is an important innate immune sensor that activates the inflammasome complex, resulting in the secretion of IL-1 beta and pyroptosis. The mechanism of NLRP3 inflammasome activation in response to crystals or particulates is unclear, but lysosomal damage has been implicated. This study discovered that apilimod, a lysosomal disruptor, is a selective and potent NLRP3 agonist that triggers mitochondrial damage and lysosomal dysfunction, leading to NLRP3 inflammasome activation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Bo Young Nam, Jong Hyun Jhee, Jimin Park, Seonghun Kim, Gyuri Kim, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Je-Wook Yu, Seung Hyeok Han
Summary: This study reveals that PGC-1 alpha-induced inactivation of the NLRP3 inflammasome, through modulation of mitochondrial viability and dynamics, can ameliorate kidney injury.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Peipei Li, Shen Li, Le Wang, Hongmin Li, Yang Wang, Hongbing Liu, Xin Wang, Xiaodan Zhu, Zhangsuo Liu, Fanglei Ye, Yuan Zhang
Summary: Sensorineural deafness is a global health problem with limited curative therapy. Mitochondrial dysfunction is found to play a vital role in the pathogenesis of deafness. Reactive oxygen species-induced mitochondrial dysfunction and activation of the NLRP3 inflammasome contribute to cochlear damage. Autophagy can help clear damaged mitochondria and excessive ROS, reducing oxidative stress, inhibiting cell apoptosis, and protecting auditory cells. The interplay between ROS generation, NLRP3 inflammasome activation, and autophagy is discussed in hearing loss caused by ototoxic drugs, noise, and aging.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Environmental Sciences
Yuming Zhang, Fengyu Yuan, Pei Li, Jihai Gu, Junjun Han, Zhihua Ni, Fengsong Liu
Summary: This study found that Resveratrol (RES) inhibits the proliferation of HeLa cells by perturbing mitochondrial structure and function, and ROS-induced autophagy plays a critical role in this process.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Cell Biology
Qianqian Di, Xibao Zhao, Haimei Tang, Xunwei Li, Yue Xiao, Han Wu, Zherui Wu, Jiazheng Quan, Weilin Chen
Summary: The research shows that USP22 inhibits the activation of NLRP3 inflammasome by promoting autophagy, and has the potential to be a therapeutic target for NLRP3 inflammasome-related diseases.
Article
Biochemistry & Molecular Biology
Ilandarage Menu Neelaka Molagoda, Athapaththu Mudiyanselage Gihan Kavinda Athapaththu, Yung Hyun Choi, Cheol Park, Cheng-Yung Jin, Chang-Hee Kang, Mi-Hwa Lee, Gi-Young Kim
Summary: The study demonstrates that Fisetin inhibits the activation of the NLRP3 inflammasome by TLR4/MD2 pathway, leading to the elimination of damaged mitochondria through p62-dependent mitophagy.
Article
Biochemistry & Molecular Biology
Lin Liu, Qingzhuo Cui, Junna Song, Yang Yang, Yixin Zhang, Jiapeng Qi, Jingshan Zhao
Summary: Inflammation is associated with vascular remodeling, and the NLRP3 inflammasome plays a crucial role in promoting vascular remodeling through VAF proliferation and differentiation. HSYA has the potential to improve vascular remodeling, but its mechanism involving inhibition of NLRP3 inflammasome activation needs further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Baoshan Cai, Jian Zhao, Yuling Zhang, Yaxing Liu, Chunhong Ma, Fan Yi, Yi Zheng, Lei Zhang, Tian Chen, Huiqing Liu, Bingyu Liu, Chengjiang Gao
Summary: USP5 acts as a key scaffold protein in recruiting the E3 ligase MARCHF7 for autophagic degradation of NLRP3 independently of its deubiquitinating enzyme activity. Knockdown of USP5 promotes inflammatory signaling release, while overexpression has inhibitory effects.
Article
Biochemistry & Molecular Biology
Yeon-Ji Park, Niranjan Dodantenna, Yonghyeon Kim, Tae-Hwan Kim, Ho-Soo Lee, Young-Suk Yoo, June Heo, Jae-Ho Lee, Myung-Hee Kwon, Ho Chul Kang, Jong-Soo Lee, Hyeseong Cho
Summary: The NLRP3 inflammasome is activated through mitochondria-mediated ubiquitination by the E3 ligase MARCH5. Knockout of MARCH5 leads to an impaired secretion of IL-1β and IL-18 in myeloid cells, as well as a decreased mortality rate upon infection. MARCH5-dependent NLRP3 ubiquitination is essential for NLRP3-NEK7 complex formation and NLRP3 oligomerization.
Article
Cell Biology
Mojca Trstenjak-Prebanda, Monika Biasizzo, Klemen Dolinar, Sergej Pirkmajer, Boris Turk, Veronique Brault, Yann Herault, Natasa Kopitar-Jerala
Summary: It has been found that increased expression of stefin B in macrophages can downregulate mitochondrial reactive oxygen species (ROS) generation, decrease inflammasome activation, increase autophagy, and potentially contribute to the development of new treatments for related diseases.
Article
Neurosciences
Yuanfeng Du, Zhangfan Lu, Dingbo Yang, Ding Wang, Li Jiang, Yongfeng Shen, Quan Du, Wenhua Yu
Summary: Activating MerTK with Gas6 alleviates brain edema, neuronal degeneration and neurological deficits after SAH by regulating neuroinflammation. Gas6 also promotes autophagic flux and neuroprotection, while inhibition of autophagy reverses the inhibition of NLRP3 inflammasome activation and diminishes the neuroprotective effects of Gas6.
Review
Biochemistry & Molecular Biology
Xuelian Li, Xianjie Zhu, Yumiao Wei
Summary: Atherosclerosis is a lipid-driven disease characterized by the imbalance between inflammatory and regressive processes. Recent studies have suggested a link between autophagy and vascular inflammation. This review summarizes the underlying mechanisms associated with different autophagic pathways and NLRP3 inflammasomes in vascular inflammation, aiming to provide additional evidence for atherosclerosis research.