Article
Multidisciplinary Sciences
Sarah E. Garnish, Yanxiang Meng, Akiko Koide, Jarrod J. Sandow, Eric Denbaum, Annette V. Jacobsen, Wayland Yeung, Andre L. Samson, Christopher R. Horne, Cheree Fitzgibbon, Samuel N. Young, Phoebe P. C. Smith, Andrew I. Webb, Emma J. Petrie, Joanne M. Hildebrand, Natarajan Kannan, Peter E. Czabotar, Shohei Koide, James M. Murphy
Summary: Phosphorylation of MLKL by RIPK3 kinase leads to MLKL oligomerization, translocation, and membrane permeabilization to induce cell death. Monobodies can bind to the MLKL pseudokinase domain, revealing distinct conformations during activation and disengagement from RIPK3, a key regulatory step in necroptosis. These structural and functional studies shed light on the mechanism of MLKL activation and regulation in necroptosis.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Cell Biology
Weiwei Qi, Junying Yuan
Summary: Super-resolution microscopy reveals the architectural features of necrosomes formed by RIPK1-RIPK3 during necroptosis, shedding light on the signaling processes from RIPK1 to RIPK3 and from RIPK3 to RIPK1 when mediating necroptosis and apoptosis, respectively.
NATURE CELL BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Xiaoyu Zhu, Xingli Xu, Chigang Du, Yanping Su, Lixue Yin, Xiaoqiu Tan, Hui Liu, Yiru Wang, Lei Xu, Xinghua Xu
Summary: Diabetic nephropathy is a leading cause of end-stage renal disease, causing significant burden on patients and society. Curcumin, a polyphenol curcuminoid, has been shown to have anti-inflammatory, antioxidative, anti-apoptotic, and anti-fibrosis properties, which are beneficial for diabetic nephropathy. Understanding the pharmacological effects of curcumin on diabetic nephropathy may lead to the development of new therapies.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Chemistry, Medicinal
Shuwei Wu, Chen Xu, Kaijiang Xia, Yu Lin, Sheng Tian, Haikuo Ma, Yuting Ji, Fang Zhu, Sudan He, Xiaohu Zhang
Summary: Novel RIPK3 inhibitors were designed, synthesized, and evaluated, with lead compound 38 showing potent activity and good selectivity and safety profiles. Compound 38 efficiently blocked cell death and demonstrated promising therapeutic effects in a mouse model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, General & Internal
Tawhidul Islam, Marta B. Afonso, Cecilia M. P. Rodrigues
Summary: Recent studies have suggested a potential link between RIPK3 and mitochondrial bioenergetics. RIPK3 can modulate mitochondrial function and quality through various mechanisms, which could have implications for chronic liver diseases. Understanding the role of RIPK3 in mitochondrial bioenergetics may lead to potential translational applications in the treatment of liver diseases.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Food Science & Technology
Yuelin Chen, Meitong Liu, Hongdi Wei, Jiakang Guo, Shengzhuo Zhang, Xiujuan Bu, Shanshan Chen, Duoduo Zhang, Shuang Guan
Summary: Excessive alcohol consumption can lead to serious liver injury, particularly through a form of programmed cell death called necroptosis. This study aimed to uncover the mechanisms behind this process and found that ethanol activates RIPK1 and RIPK3, leading to necroptosis in hepatocytes. Additionally, autophagy was activated in ethanol-treated hepatocytes. The researchers also discovered that LC3, an autophagy marker protein, plays a crucial role in ethanol-induced necroptosis. Knocking down LC3 or using an autophagy inhibitor alleviated necrosome formation and necroptosis in hepatocytes. These findings provide new insights into the complex mechanisms involved in the development of acute alcoholic liver injury.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Cell Biology
Shufen Li, Yulan Zhang, Zhenqiong Guan, Meidi Ye, Huiling Li, Miaomiao You, Zhenxing Zhou, Chongtao Zhang, Fan Zhang, Ben Lu, Peng Zhou, Ke Peng
Summary: SARS-CoV-2 infection induces the formation of viral Z-RNA, leading to activation of the ZBP1-RIPK3 pathway and subsequent inflammatory responses. Inhibition of RIPK3 or deletion of MLKL reduces IL-1 beta release caused by SARS-CoV-2 infection. Deficiency of ZBP1 or RIPK3 reduces the production of inflammatory cytokines and chemokines, immune cell infiltration, and lung damage in SARS-CoV-2 infected models. Targeting the ZBP1-RIPK3 axis may have therapeutic potential in treating COVID-19.
Article
Multidisciplinary Sciences
Xia-Lian Wu, Hong Hu, Xing-Qi Dong, Jing Zhang, Jian Wang, Charles D. Schwieters, Jing Liu, Guo-Xiang Wu, Bing Li, Jing-Yu Lin, Hua-Yi Wang, Jun-Xia Lu
Summary: RIPK3 amyloid complex is vital in TNF-induced necroptosis and immune defense, with a well-ordered N-shaped structure featuring 3 parallel in-register beta-sheets. RIPK1-RIPK3 binding and RIPK3 amyloid formation are both necessary for necroptosis, while the structural integrity of the RIPK3 fibril with three beta-strands is crucial for signaling. Structural transformation from RIPK1-RIPK3 binding to RIPK3 amyloid formation is a key step in connecting these processes.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
John D. Lyons, Pratyusha Mandal, Shunsuke Otani, Deena B. Chihade, Kristen F. Easley, David A. Swift, Eileen M. Burd, Zhe Liang, Michael Koval, Edward S. Mocarski, Craig M. Coopersmith
Summary: Deletion or mutation of RIPK3 reduces inflammation and mortality in mice with Pseudomonas pneumonia. RIPK3 kinase activity is dispensable for cell killing but is involved in cytokine production. The RIPK3 scaffold domain mediates deleterious inflammation and may be a target for reducing lung inflammation during infection.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Daniel Frank, Sarah E. Garnish, Jarrod J. Sandow, Ashley Weir, Lin Liu, Elise Clayer, Lizeth Meza, Maryam Rashidi, Simon A. Cobbold, Simon R. Scutts, Marcel Doerflinger, Holly Anderton, Kate E. Lawlor, Najoua Lalaoui, Andrew J. Kueh, Vik Ven Eng, Rebecca L. Ambrose, Marco J. Herold, Andre L. Samson, Rebecca Feltham, James M. Murphy, Gregor Ebert, Jaclyn S. Pearson, James E. Vince
Summary: This study reveals that RIPK3 is ubiquitylated on K469, which can limit RIPK3-mediated apoptosis and necroptosis. Mutations in other ubiquitylated residues of RIPK3 increase RIPK3 hyper-ubiquitylation and cell death.
Review
Biochemistry & Molecular Biology
Shanhui Liu, Kanak Joshi, Mitchell F. Denning, Jiwang Zhang
Summary: RIPK3 is a serine/threonine-protein kinase that plays key roles in inflammation and necrosis, potentially with different effects in cancer pathogenesis. It is involved in regulating various cellular processes such as apoptosis, mitochondrial metabolism, and cell proliferation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Wenxian Wu, Xiaojing Wang, Yadong Sun, Niklas Berleth, Jana Deitersen, David Schluetermann, Fabian Stuhldreier, Nora Wallot-Hieke, Maria Jose Mendiburo, Jan Cox, Christoph Peter, Ann Kathrin Bergmann, Bjoern Stork
Summary: This study identified RIPK3 as an AMPK-activating kinase, establishing a direct link between the kinases regulating autophagy and necroptosis.Activation of AMPK by RIPK3 leads to phosphorylation of autophagy-regulating proteins ULK1 and BECN1, while TNF-induced necroptosis blocks lysosomal degradation of autophagosomes. Dysregulation of SNARE complexes, including reduced levels of full-length STX17, was observed upon TNF treatment.
Article
Multidisciplinary Sciences
Xialian Wu, Yeyang Ma, Kun Zhao, Jing Zhang, Yunpeng Sun, Yichen Li, Xingqi Dong, Hong Hu, Jing Liu, Jian Wang, Xia Zhang, Bing Li, Huayi Wang, Dan Li, Bo Sun, Junxia Lu, Cong Liu
Summary: RIPK3, a key protein involved in necroptosis, forms amyloid fibrils via its RHIM domain. The study determined the fibril structure of RIPK3 C-terminal domain containing RHIM using cryo-EM and solid-state NMR. The unique assembly of RIPK3-CTD fibril may contribute to efficient phosphorylation of RIPK3 kinase domain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Kaibo Hu, Ruifeng He, Minxuan Xu, Deju Zhang, Guangyu Han, Shengye Han, Leyang Xiao, Panpan Xia, Jitao Ling, Tingyu Wu, Fei Li, Yunfeng Sheng, Jing Zhang, Peng Yu
Summary: Through experiments, we identified the necroptosis in DN and built a necroptosis-mediated diagnostic model based on this new discovery, providing new insights into the diagnosis and treatment of diabetic nephropathy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xiao-yan He, Fang Wang, Xiao-guo Suo, Ming-zhen Gu, Jia-nan Wang, Chuan-hui Xu, Yu-hang Dong, Yuan He, Yao Zhang, Ming-lu Ji, Ying Chen, Meng-meng Zhang, Yin-guang Fan, Jia-gen Wen, Juan Jin, Jie Wang, Jun Li, Chun-lin Zhuang, Ming-ming Liu, Xiao-ming Meng
Summary: The novel RIPK3 inhibitor, Cpd-42, reduces kidney damage and necroptosis in acute kidney injury by binding to specific sites on RIPK3. It shows promise as a potential treatment for acute kidney injury.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)