Article
Cell Biology
Inbar Shlomovitz, Ziv Erlich, Gali Arad, Liat Edry-Botzer, Sefi Zargarian, Hadar Cohen, Tal Manko, Yifat Ofir-Birin, Tomer Cooks, Neta Regev-Rudzki, Motti Gerlic
Summary: Necroptotic extracellular vesicles contain a specific protein composition that can be phagocytosed by macrophages, influencing cytokine and chemokine secretion. Additionally, these EVs contain tumor neoantigens and components of antigen processing and presentation.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Tamas Molnar, Petra Pallagi, Balint Tel, Robert Kiraly, Eszter Csoma, Viktoria Jenei, Zsofia Varga, Peter Gogolak, Anne Odile Hueber, Zoltan Mate, Ferenc Erdelyi, Gabor Szabo, Aladar Pettko-Szandtner, Attila Bacsi, Laszlo Virag, Jozsef Maleth, Gabor Koncz
Summary: Necroptosis is a regulated type of cell death that acts as a backup mechanism when apoptosis is inhibited or absent, and it is associated with the pathogenesis of various diseases and tumor regulation. The research found that Caspase-9 serves as a newly identified regulator of Necroptosis, offering a promising therapeutic target for manipulating the immunological outcome of cell death.
Article
Pharmacology & Pharmacy
Serena Castelli, Enrico Desideri, Maria Rosa Ciriolo
Summary: Hepatocellular carcinoma (HCC) is a common and deadly cancer. This study demonstrates that a compound called glycyl-l-phenylalanine 2-naphthylamide (GPN) can induce cell death in HCC cell lines through a caspase-independent mechanism. The MAPK p38 is identified as a novel mediator of the lysosomal stress response. Inhibition of p38 increases cell death caused by GPN. These findings suggest that targeting p38 may enhance the cytotoxic effects of lysosomal damage and induce caspase-independent cell death in HCC cells, providing a potential strategy for combination therapy.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Cell Biology
Ke Lu, Si-Yu Shen, Ou-Yang Luo, Yue Lu, Tian-Shu Shi, Jing Wu, Qi Cheng, Hua-Jian Teng, Di Chen, Xiang Lu, Chao-Jun Li, Qing Jiang, Lei Fang, Bin Xue
Summary: In the Carbon tetrachloride (CCl4)-induced acute liver injury (ALI) mouse model, targeting PP2Ac alpha to favor apoptotic cell fate can reduce liver damage and improve liver function. Disruption of PP2Ac alpha prevents CCl4-induced liver injury and fibrogenesis by inhibiting the ASK/JNK pathway mediated programmed cell death (PCD) signaling. Biasing hepatocytes towards an apoptotic rather than necroptotic cell fate may represent an attractive therapeutic strategy for treating ALI.
CELL DEATH & DISEASE
(2022)
Review
Immunology
Ashley Weir, Sebastian Hughes, Maryam Rashidi, Joanne M. Hildebrand, James E. Vince
Summary: The necroptotic cell death pathway and the role of MLKL in triggering inflammatory responses have been studied extensively. MLKL has diverse functions contributing to the inflammatory nature of necroptosis. MLKL-driven responses activate inflammasome complexes and innate lymphoid cells, leading to disease progression.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Gastroenterology & Hepatology
Ping Sun, Jie Zhong, Hong Liao, Patricia Loughran, Joud Mulla, Guang Fu, Da Tang, Jie Fan, Timothy R. Billiar, Wentao Gao, Melanie J. Scott
Summary: This study found that hepatocytes can activate pyroptosis pathways and cleave gasdermin-D (GSDMD), but unlike macrophages, pyroptotic hepatocytes do not exhibit significant cell rupture and morphological changes. These findings have important implications for understanding and recognizing the role of these pathways in hepatocytes, and may lead to the development of novel therapeutics for liver diseases.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kakali Bhadra
Summary: This article reviews the alternative pathways of cancer cell death targeted by anticancer drug molecules, providing a molecular basis for new strategies in cancer treatment. Many drugs can effectively induce cell death through targeting the caspase-independent cell death pathway, which is significant for cancer therapy.
Article
Cell Biology
Arindam Mondal, Jacques Roberge, John Gilleran, Youyi Peng, Dongxuan Jia, Moumen Akel, Yash Patel, Harrison Zoltowski, Anupama Doraiswamy, John Langenfeld
Summary: This study reveals that inhibition of BMP signaling combined with mitochondrial targeting agents induces AIF caspase-independent cell death, primarily through the hyperactivation of AMPK. This is an infrequently studied cell death pathway in cancer.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Leo Razakamanantsoa, Neeraj R. Rajagopalan, Yasushi Kimura, Michele Sabbah, Isabelle Thomassin-Naggara, Francois H. Cornelis, Govindarajan Srimathveeravalli
Summary: Irreversible electroporation (IRE) can cause apoptosis, necrosis, oncosis, or pyroptosis. The mode of cell death following IRE is determined by intracellular ATP levels. Cell death after IRE is insensitive to caspase inhibition and is correlated with ATP loss, which cannot be rescued by ATP supplementation.
BIOELECTROCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Patrick Niekamp, Felix Scharte, Tolulope Sokoya, Laura Vittadello, Yeongho Kim, Yongqiang Deng, Elisabeth Sudhoff, Angelika Hilderink, Mirco Imlau, Christopher J. Clarke, Michael Hensel, Christopher G. Burd, Joost C. M. Holthuis
Summary: Cells use a sphingomyelin-based lysosomal repair pathway to reverse potentially lethal membrane damage, independently of ESCRT function. Activation of scramblases, sphingomyelin, and neutral sphingomyelinases helps preserve the functional integrity of lysosomes.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Min Chen, Lei Wang, Min Li, Marietta M. Budai, Jin Wang
Summary: Mitochondrial disruption can lead to cell death through caspase-9 activation. However, cell death can also occur independently of caspase-9, suggesting the existence of caspase-9-independent cell death mechanisms. Through a genome-wide siRNA library screening, researchers identified a network of genes that mediate caspase-9-independent cell death through ROS production and Alox5-dependent membrane lipid peroxidation. The Erk1-Alox5 pathway plays a critical role in promoting membrane lipid peroxidation and nuclear translocation of cytolytic molecules, resulting in cell death.
Article
Immunology
Eric J. Gapud, Maria Isabel Trejo-Zambrano, Eduardo Gomez-Banuelos, Eleni Tiniakou, Brendan Antiochos, David J. Granville, Felipe Andrade, Livia Casciola-Rosen, Antony Rosen
Summary: This study unveils a range of novel signaling activities of Granzyme B that do not require perforin, occur intracellularly, and are not associated with cell death, which could have mechanistic implications for human diseases.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Zhiqin Deng, Huangcan Li, Shu Chen, Na Wang, Gongyuan Liu, Danjun Liu, Weihui Ou, Feijie Xu, Xiong Wang, Dangyuan Lei, Pui-Chi Lo, Yang Yang Li, Jian Lu, Mengsu Yang, Ming-Liang He, Guangyu Zhu
Summary: This study reports the use of near-infrared-activated small-molecule Pt(IV) photooxidants to directly oxidize intracellular biomolecules. These photooxidants can effectively eliminate cancer stem cells and show low toxicity in the dark. Metal-enhanced photooxidation induced by these Pt(IV) complexes leads to robust photooxidation of survival-related biomolecules, inducing oxidative stress, disrupting intracellular pH (pHi) homeostasis, and initiating nonclassical necrosis.
Article
Food Science & Technology
Simin Chen, Claudia Figueiredo Lossio, Isabel Verbeke, Joost Verduijn, Bogdan Parakhonskiy, Louis Van der Meeren, Pengyu Chen, Jeroen De Zaeytijd, Andre G. Skirtach, Els J. M. Van Damme
Summary: The study found that OsRIP1 can inhibit protein synthesis in a sustained manner, leading to reduced proliferation of HeLa cells with apoptotic-like changes in the cell membrane, but without causing DNA fragmentation. OsRIP1 also interacts with ASPP1 and IFITM3, causing changes in the transcription levels of important genes in the cells, inducing a caspase-independent cell death process in HeLa cells.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Neurosciences
Narjes Shahsavani, Arsalan Alizadeh, Hardeep Kataria, Soheila Karimi-Abdolrezaee
Summary: Nrg-1131 provides early neuroprotection in SCI by reducing oxidative stress, lipid peroxidation, necrosis, and apoptosis. Mechanistically, it protects neurons from cell death by modulating mitochondrial-associated apoptotic cascades, MAP kinase, and AKT signaling pathways.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Developmental Biology
Xia Liu, Satoru Hayano, Haichun Pan, Maiko Inagaki, Jun Ninomiya-Tsuji, Hongchen Sun, Yuji Mishina
Correction
Multidisciplinary Sciences
September R. Mihaly, Yosuke Sakamachi, Jun Ninomiya-Tsuji, Sho Morioka
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Sho Morioka, Justin S. A. Perry, Michael H. Raymond, Christopher B. Medina, Yunlu Zhu, Liyang Zhao, Vlad Serbulea, Suna Onengut-Gumuscu, Norbert Leitinger, Sarah Kucenas, Jeffrey C. Rathmell, Liza Makowski, Kodi S. Ravichandran
Article
Cell & Tissue Engineering
Hsiao Hsin Sung Hsieh, Shailesh Agarwal, David J. Cholok, Shawn J. Loder, Kieko Kaneko, Amanda Huber, Michael T. Chung, Kavitha Ranganathan, Joe Habbouche, John Li, Jonathan Butts, Jonathan Reimer, Arminder Kaura, James Drake, Christopher Breuler, Caitlin R. Priest, Joe Nguyen, Cameron Brownley, Jonathan Peterson, Serra Ucer Ozgurel, Yashar S. Niknafs, Shuli Li, Maiko Inagaki, Greg Scott, Paul H. Krebsbach, Michael T. Longaker, Kenneth Westover, Nathanael Gray, Jun Ninomiya-Tsuji, Yuji Mishina, Benjamin Levi
Review
Immunology
Sho Morioka, Christian Maueroder, Kodi S. Ravichandran
Article
Cell Biology
Kazuhito Sai, Cameron Parsons, John S. House, Sophia Kathariou, Jun Ninomiya-Tsuji
JOURNAL OF CELL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Claudia M. Rival, Wenhao Xu, Laura S. Shankman, Sho Morioka, Sanja Arandjelovic, Chang Sup Lee, Karen M. Wheeler, Ryan P. Smith, Lisa B. Haney, Brant E. Isakson, Scott Purcell, Jeffrey J. Lysiak, Kodi S. Ravichandran
NATURE COMMUNICATIONS
(2019)
Article
Cell Biology
Justin S. A. Perry, Sho Morioka, Christopher B. Medina, J. Iker Etchegaray, Brady Barron, Michael H. Raymond, Christopher D. Lucas, Suna Onengut-Gumuscu, Eric Delpire, Kodi S. Ravichandran
NATURE CELL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Christopher B. Medina, Parul Mehrotra, Sanja Arandjelovic, Justin S. A. Perrys, Yizhan Guo, Sho Morioka, Brady Barron, Scott F. Walk, Bart Ghesquiere, Ulrike Lorenz, Alexander S. Krupnick, Kodi S. Ravichandran
Article
Multidisciplinary Sciences
Wilfred Lopez-Perez, Kazuhito Sai, Yosuke Sakamachi, Cameron Parsons, Sophia Kathariou, Jun Ninomiya-Tsuji
Summary: Inhibition of TAK1 induces the production of ROS, which effectively destroys intracellular bacteria. This mechanism initiates a host defense response by recognizing the impairment of TAK1 by pathogens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Michael H. Raymond, Andrew J. Davidson, Yi Shen, Daniel R. Tudor, Christopher D. Lucas, Sho Morioka, Justin S. A. Perry, Julia Krapivkina, David Perrais, Linus J. Schumacher, Robert E. Campbell, Will Wood, Kodi S. Ravichandran
Summary: By utilizing the CharON reporter, it was found that in the embryonic development of Drosophila, emerging apoptotic cells are cleared by macrophages, but some macrophages may carry a high corpse burden, affecting their ability to clear wound debris.
Article
Biochemistry & Molecular Biology
Sho Morioka, Daiki Kajioka, Yusuke Yamaoka, Rochelle M. Ellison, Turan Tufan, Inge L. Werkman, Shinji Tanaka, Brady Barron, Satoshi T. Ito, Sarah Kucenas, Mark D. Okusa, Kodi S. Ravichandran
Summary: Defects in efferocytosis are linked to inflammatory diseases. A strategy called chimeric receptor for efferocytosis (CHEF) is designed to boost efferocytosis and reduce inflammation.
Review
Urology & Nephrology
Yohei Arai, Yusuke Yamaoka, Sho Morioka
Summary: Research has identified various forms of cell death, and clearing dead cells is crucial for maintaining tissue homeostasis. It is unknown whether enhancing the removal of specific types of dying cells would be beneficial. Due to the lack of viable strategies for the prevention and treatment of acute kidney injury, novel therapies and innovative approaches are needed.
Article
Oncology
Alex D. Michaels, Timothy E. Newhook, Sara J. Adair, Sho Morioka, Bernadette J. Gaudreau, Sarbajeet Nagdas, Matthew G. Mullen, Jesse B. Persily, Timothy N. J. Bullock, Craig L. Slingluff, Kodi S. Ravichandran, J. Thomas Parsons, Todd W. Bauer
CLINICAL CANCER RESEARCH
(2018)