Article
Immunology
Aiting Wang, Lei Ding, Zhongqiu Wu, Rui Ding, Xiao-Lu Teng, Feixiang Wang, Zhilin Hu, Lei Chen, Xiaoyan Yu, Qiang Zou
Summary: This study demonstrates that the E3 ubiquitin ligase ZFP91 promotes autophagy activation in regulatory T cells, maintaining their metabolic programming and functional integrity. Deletion of Zfp91 in T cells leads to dysfunction and exacerbates colonic inflammation and inflammation-driven colon cancer. TCR-triggered autophagy induction relies on T cell-derived ZFP91 to restrict hyperglycolysis for cell homeostasis maintenance.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Hyunju Oh, Jingyao Zhao, Yenkel Grinberg-Bleyer, Thomas S. Postler, Pingzhang Wang, Sung-Gyoo Park, Raul Rabadan, Matthew S. Hayden, Sankar Ghosh
Summary: This study demonstrates the essential role of PDK1 in both T cell activation and Treg cell suppressive activity, with PDK1 regulating Treg cell gene expression and suppressor function primarily through the NF-κB pathway.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yumei Jia, Zhaoyuan Guo, Jiahao Zhu, Guanyu Qin, Wenwen Sun, Yu Yin, Haiying Wang, Renpeng Guo
Summary: The study shows that Snap29 plays a crucial role in the self-renewal and differentiation of mouse ESCs. Depletion of Snap29 does not affect the self-renewal and pluripotency-associated factor expression in ESCs, but enhances their differentiation into cardiomyocytes. Transcriptome analysis reveals that Snap29 deficiency significantly decreases the expression of genes required for germ layer differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sylwia M. Kacprzak, Olivier Van Aken
Summary: Mitochondria play vital roles in plant metabolism and stress responses. Quality control systems, including mitophagy, are important for maintaining a healthy mitochondrial pool. The 'Friendly Mitochondria' protein (FMT) has been identified as a crucial player in mitophagy during dark-induced senescence in Arabidopsis.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Liu Yang, Haiyan Yang, Yunxiang Chu, Yunhao Song, Lidan Ding, Bingtao Zhu, Wanli Zhai, Xuning Wang, Yanshen Kuang, Fangli Ren, Baoqing Jia, Wei Wu, Xiongjun Ye, Yinyin Wang, Zhijie Chang
Summary: This study reveals the essential role of CREPT in maintaining murine intestinal stem cells, with its deficiency impairing cell proliferation and regeneration. The downregulation of Wnt signaling due to CREPT deletion is identified as a key mechanism affecting ISC function.
NATURE COMMUNICATIONS
(2021)
Article
Endocrinology & Metabolism
Ben Vanderkruk, Nina Maeshima, Daniel J. Pasula, Meilin An, Cassandra L. McDonald, Priya Suresh, Dan S. Luciani, Francis C. Lynn, Brad G. Hoffman
Summary: This study finds that H3K4 methylation is essential for the maintenance of mature beta cell function, and the redistribution of H3K4me3 is closely related to gene expression changes implicated in diabetes pathology.
Article
Immunology
Niels C. Lory, Mikolaj Nawrocki, Martina Corazza, Joanna Schmid, Valea Schumacher, Tanja Bedke, Stephan Menzel, Friedrich Koch-Nolte, Andreas H. Guse, Samuel Huber, Hans-Willi Mittruecker
Summary: This study investigates the function of TRPM2 in T-cell activation and differentiation using TRPM2-deficient mice. The results suggest that TRPM2 does not play a major role in T-cell activation and differentiation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Hang Liu, Chenran Wang, Fei Yi, Syn Yeo, Michael Haas, Xin Tang, Jun-Lin Guan
Summary: The non-canonical functions of FIP200 are essential for regulating mouse NSC maintenance and neurogenesis by limiting TBK1 activation and p62 aggregate formation.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Adel Hammoutene, Marion Tanguy, Melanie Calmels, Riccardo Pravisani, Miguel Albuquerque, Christophe Casteleyn, Lotfi Slimani, Jeremy Sadoine, Chantal M. Boulanger, Valerie Paradis, Helene Gilgenkrantz, Pierre-Emmanuel Rautou
Summary: Patients with non-alcoholic fatty liver disease (NAFLD) have impaired liver regeneration due to a defect in autophagy of liver endothelial cells. This study aimed to determine the role of endothelial autophagy in liver regeneration following liver resection in NAFLD.
LIVER INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Jonathan Ribeiro, Gerry P. Crossan
Summary: Recycling and de-novo deposition of histones during DNA replication is coordinated by histone chaperones. Here, we demonstrate the role of a germ cell specific histone chaperone, GCNA, in the maintenance of undifferentiated spermatogonia (USGs) in mice. Our findings provide a mechanistic basis for male infertility caused by GCNA mutations.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Immunology
Constantin Schmidt, Aenne Harberts, Daniel Reimers, Tabea Bertram, Leonie Caroline Voss, Joanna Schmid, Niels Christian Lory, Michael Spohn, Friedrich Koch-Nolte, Samuel Huber, Friederike Raczkowski, Minka Breloer, Hans-Willi Mittruecker
Summary: The transcription factor IRF4 plays a central role in controlling T cell activation and differentiation. Deficiency of IRF4 results in severe immune deficiency, impaired T cell maturation and function, and compromised control of pathogens. The study shows that IRF4 is vital for Th17 and Th2 cell responses and the recruitment of T helper cells to the intestine. IRF4 regulates the expression of intestinal homing receptors and is essential for Th2 and Th17 cell differentiation and migration to the intestine.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rachel Curnock, Katy Yalci, Johan Palmfeldt, Marja Jaattela, Bin Liu, Bernadette Carroll
Summary: The accumulation of senescent cells is a driver of aging, and one characteristic of senescent cells is an increase in lysosomal content. However, little is known about the causes and consequences of lysosomal biogenesis in senescence.
Article
Biochemistry & Molecular Biology
Shinya Aramaki, Saya Kagiwada, Guangming Wu, David Obridge, Kenjiro Adachi, Eva Kutejova, Heiko Lickert, Karin Huebner, Hans R. Schoeler
Summary: The mesodermal transcription factor T has a global effect on pluripotency by binding to Oct4 and other pluripotency regulators, affecting cell differentiation pathways. Lower T levels promote germ cell differentiation, while higher levels enhance somatic differentiation and repress germ cell differentiation. In vivo, nascent germ cells are detected in areas with lower T levels, indicating a regulatory mechanism for germ cell segregation from somatic lineages.
Article
Biochemistry & Molecular Biology
Qingnan Tian, Yujia Sun, Tingting Gao, Jiaxin Li, Huimin Fang, Shoutao Zhang
Summary: SUMOylation and ubiquitylation are crucial processes in eukaryotic biology, with Djubc9 and Djnedd4L identified as important factors in head regeneration in planarians through RNA-seq analysis. RNA interference experiments confirmed their roles in stem cell maintenance and regeneration processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yuanjun Li, Yonglu Tian, Xiayuhe Pei, Pengli Zheng, Linqing Miao, Lingjun Li, Chunxiong Luo, Peixun Zhang, Baoguo Jiang, Junlin Teng, Ning Huang, Jianguo Chen
Summary: Proper microtubule dynamics are crucial for neuronal morphogenesis and functions. This study shows that Scg10 knockout mice exhibit severe motor and sensory dysfunctions, with deficits in nerve myelination and neuromuscular degeneration. The study also suggests that SCG10 plays an important role in axon maintenance and regeneration by regulating microtubule dynamics.
JOURNAL OF CELL SCIENCE
(2023)
Review
Cell Biology
Celine Deneubourg, Mauricio Ramm, Luke J. Smith, Olga Baron, Kritarth Singh, Susan C. Byrne, Michael R. Duchen, Mathias Gautel, Eeva-Liisa Eskelinen, Manolis Fanto, Heinz Jungbluth
Summary: Primary dysfunction of autophagy due to Mendelian defects affecting core components of the autophagy machinery or closely related proteins has been recognized as an important cause of genetic disease. These disorders can present throughout life, with severe early-onset neurodevelopmental disorders and more common adult-onset neurodegenerative disorders. The overlap between congenital autophagy disorders and other multisystem diseases reflects the complex roles of proteins and suggests a promising area for future research.
Article
Gastroenterology & Hepatology
Mansi Arora, James M. Bogenberger, Amro M. Abdelrahman, Jennifer Yonkus, Roberto Alva-Ruiz, Jennifer L. Leiting, Xianfeng Chen, Pedro Luiz Serrano Uson, Chelsae R. Dumbauld, Alexander T. Baker, Scott Gamb, Jan B. Egan, Yumei Zhou, Bolni Marius Nagalo, Nathalie Meurice, Eeva-Liisa Eskelinen, Marcela A. Salomao, Heidi E. Kosiorek, Esteban Braggio, Michael T. Barrett, Kenneth H. Buetow, Mohamad B. Sonbol, Aaron S. Mansfield, Lewis R. Roberts, Tanios S. Bekaii-Saab, Daniel H. Ahn, Mark J. Truty, Mitesh J. Borad
Summary: The combination of gemcitabine/cisplatin and CDK4/6 inhibitors showed enhanced efficacy, reduced toxicity, and better survival in BTC models. Monotherapy with abemaciclib had modest efficacy due to autophagy-induced resistance, but triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Abemaciclib also potentiated sensitization to gemcitabine through reduction of ribonucleotide reductase catalytic subunit M1.
Article
Immunology
Iwona T. Myszor, Snaevar Sigurdsson, Alexia Ros Viktorsdottir, Birgitta Agerberth, Eeva-Liisa Eskelinen, Margret Helga Ogmundsdottir, Gudmundur H. Gudmundsson
Summary: This study found that APD HO53 induces autophagy through a complex mechanism involving multiple pathways and epigenetic events. The induction of autophagy is associated with activation of AMPK, nuclear translocation of TFEB, and changes in expression of autophagy-related genes.
JOURNAL OF INNATE IMMUNITY
(2022)
Article
Multidisciplinary Sciences
Tanja Buchacher, Anni Honkimaa, Tommi Valikangas, Niina Lietzen, M. Karoliina Hirvonen, Jutta E. Laiho, Amir-Babak Sioofy-Khojine, Eeva-Liisa Eskelinen, Heikki Hyoty, Laura L. Elo, Riitta Lahesmaa
Summary: Enteroviruses, especially group B coxsackieviruses (CVBs), have been linked to the development of type 1 diabetes. However, the mechanisms behind persistent enterovirus infection and beta cell autoimmunity are not fully understood. This study established a persistent infection model using two CVB1 strains in a human pancreatic cell line and observed changes in gene expression related to the pancreatic microenvironment, secretory pathway, and lysosomal biogenesis. The antiviral response pathways were also found to be differently activated by the two strains.
Article
Cell Biology
Fangyang Wang, Ying Yang, Gabriel Boudagh, Eeva-Liisa Eskelinen, Daniel J. Klionsky, Sami N. Malek
Summary: The discovery of mutations in V-ATPase subunits and regulators in follicular lymphoma highlights the role of autophagy, amino acid, and nutrient-sensing pathways in the disease's pathogenesis. Novel mutations in the ER-resident chaperone VMA21 lead to mislocalization of VMA21 and impairment in V-ATPase activity, resulting in amino acid depletion and compensatory autophagy activation.
Article
Cell Biology
Mahmud O. Abdullah, Run X. Zeng, Chelsea L. Margerum, David Papadopoli, Cian Monnin, Kaylee B. Punter, Charles Chu, Mohammad Al-Rofaidi, Naser F. Al-Tannak, Domenica Berardi, Zahra Rattray, Nicholas J. W. Rattray, Sheela A. Abraham, Eeva-Liisa Eskelinen, David G. Watson, Daina Avizonis, Ivan Topisirovic, Edmond Y. W. Chan
Summary: The relationship between nutrient starvation and mitochondrial dynamics is poorly understood. In this study, researchers found that cells undergoing amino acid starvation show mitochondrial fusion as a response to evade mitophagy, and supplementation of glutamine, leucine, and arginine further enhances this mitochondrial fusion. The fusion response is dependent on mitochondrial fusion proteins Mfn1 and Opa1 but independent of MTORC1. Metabolite profiling indicates that the supplementation replenishes amino acid and nucleotide pools, and inhibition of fumarate hydra-tase, glutaminolysis, or inosine monophosphate dehydrogenase blocks the mitochondrial hyperfusion, suggesting the critical roles of the tricarboxylic acid (TCA) cycle and purine biosynthesis in this response. Metabolic tracer analyses support the idea that supplemented glutamine promotes purine biosynthesis by serving as a donor of amine groups. This study provides insights into a metabolic mechanism that directly senses cellular amino acids to control mitochondrial fusion and cell fate.
Article
Pharmacology & Pharmacy
Stavroula Zagkou, Valentine Marais, Narimane Zeghoudi, Edouard Le Guillou, Eeva-Liisa Eskelinen, Ganna Panasyuk, Bernard Verrier, Charlotte Primard
Summary: This study aimed to design autophagy-inducing particles for the treatment of NAFLD. The results showed that these particles were able to effectively induce autophagy and reduce intracellular lipid in vitro. They also exhibited promising liver targeting in normal and obese mice.
Article
Cell Biology
Jia Le Lee, Sigrid C. Fra-Bido, Alice R. Burton, Silvia Innocentin, Danika L. Hill, Michelle A. Linterman
Summary: This study finds that B cells from aged individuals are not intrinsically defective in responding to stimulation and becoming antibody-secreting cells, but rather it is caused by B cell-extrinsic factors leading to a decline in the immune system's antibody response.
Editorial Material
Cell Biology
Suresh Kumar, Ruheena Javed, Masroor A. A. Paddar, Eeva-Liisa Eskelinen, Graham S. Timmins, Vojo Deretic
Summary: Mammalian autophagosomes form from a hybrid membrane compartment known as a prophagophore or HyPAS, which originates from preexisting membranes and undergoes lipid transfer and fusion with lysosomes. The formation of the prophagophore involves fusion of RB1CC1/FIP200-containing vesicles from the cis-Golgi with endosomally derived ATG16L1 membranes, and is regulated by a Ca2+-responsive apparatus. The process of autophagic prophagophore formation is inhibited during SARS-CoV-2 infection and can be replicated by expressing SARS-CoV-2 nsp6. These findings highlight the convergence of secretory and endosomal pathways in the formation of mammalian autophagosomal prophagophores and the influence of microbial factors.
Article
Cell Biology
William S. Foster, Jia Le Lee, Nazia Thakur, Joseph Newman, Alexandra J. Spencer, Sophie Davies, Danielle Woods, Leila Godfrey, Iain M. Hay, Silvia Innocentin, Juan Carlos Yam-Puc, Emily C. Horner, Hayley J. Sharpe, James E. Thaventhiran, Dalan Bailey, Teresa Lambe, Michelle A. Linterman
Summary: This study demonstrates the critical role of germinal centers induced by the ChAdOx1 nCoV-19 vaccine in humoral immunity, with T follicular helper (Tfh) cells playing an important role and exhibiting pluripotent memory.
CELL REPORTS MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ruheena Javed, Ashish Jain, Thabata Duque, Emily Hendrix, Masroor Ahmad Paddar, Sajjad Khan, Aurore Claude-Taupin, Jingyue Jia, Lee Allers, Fulong Wang, Michal Mudd, Graham Timmins, Keith Lidke, Tor Erik Rusten, Prithvi Reddy Akepati, Yi He, Fulvio Reggiori, Eeva-Liisa Eskelinen, Vojo Deretic
Summary: This study reveals that autophagosomal membranes become permeable and fail to mature into autolysosomes in cells lacking principal ATG8 proteins (mATG8s). It further uncovers a previously unknown function of mATG8s in maintaining the sealed state of autophagosomal membranes. The binding of mATG8 proteins GABARAP and LC3A to key ESCRT-I components contributes to the integrity and impermeability of autophagic membranes.
Article
Biochemistry & Molecular Biology
Agatha C. van der Klaauw, Emily Horner, Pehuen Pereyra-Gerber, Utkarsh S. Agrawal, William Foster, Sarah Spencer, Bensi Vergese, Miriam Smith, Elana D. Henning, Isobel A. Ramsay, Jack M. Smith, Stephane J. Guillaume, Hayley M. Sharpe, Iain Hay, Sam Thompson, Silvia H. Innocentin, Lucy Booth, Chris Robertson, Colin McCowan, Steven Kerr, Thomas J. Mulroney, Martin P. O'Reilly, Thevinya P. Gurugama, Lihinya A. Gurugama, Maria Rust, Alex Ferreira, Soraya Ebrahimi, Lourdes Ceron-Gutierrez, Jacopo Scotucci, Barbara J. Kronsteiner, Susanna Dunachie, Paul J. Klenerman, Adrian A. Park, Francesco Rubino, Abigail Lamikanra, Hannah Stark, Nathalie Kingston, Lise Estcourt, Heli Harvala, David A. Roberts, Rainer J. Doffinger, Michelle Linterman, Nicholas Matheson, Aziz Sheikh, I. Sadaf Farooqi, James E. D. Thaventhiran
Summary: Obesity is associated with an increased risk of severe COVID-19 infection and mortality. COVID-19 vaccines may be less effective in individuals with obesity. A study in Scotland found that vaccinated individuals with severe obesity were more likely to experience hospitalization or death from COVID-19. Another study found that individuals with severe obesity had lower levels of neutralizing antibodies after vaccination compared to individuals with a normal BMI, and the decline in antibody levels was faster in people with severe obesity.
Editorial Material
Cell Biology
Eric Chevet, Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Hesso Farhan
Review
Biochemistry & Molecular Biology
Eeva-Liisa Eskelinen
Summary: The generation of autophagosomes is a long-standing question in the field of autophagy. Recent studies using cryo-electron tomography and detailed analysis of image data have revealed new information on the membrane dynamics of autophagosome biogenesis, including the shape and dimensions of omegasomes, phagophores, and autophagosomes, and their relationships with surrounding organelles. An important prediction from these findings is that 60-80% of the autophagosome membrane area is obtained through direct lipid transfer or lipid synthesis. Cryo-electron tomography is expected to provide new directions for autophagy research in the future.
Editorial Material
Cell Biology
Eric Chevet, Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Hesso Farhan