Article
Biochemistry & Molecular Biology
Alessio Reggio, Viviana Buonomo, Rayene Berkane, Ramachandra M. Bhaskara, Mariana Tellechea, Ivana Peluso, Elena Polishchuk, Giorgia Di Lorenzo, Carmine Cirillo, Marianna Esposito, Adeela Hussain, Antje K. Huebner, Christian A. Hubner, Carmine Settembre, Gerhard Hummer, Paolo Grumati, Alexandra Stolz
Summary: The degradation of the endoplasmic reticulum via selective autophagy is crucial for cellular homeostasis. FAM134A and FAM134C have been identified as ER-phagy receptors that can induce ER fragmentation and lysosomal degradation. The FAM134 paralogues play a significant role in maintaining ER morphology and increasing ER-phagy flux.
Article
Multidisciplinary Sciences
Liang Hao, Yu-Yi Ling, Zhi-Xin Huang, Zheng-Yin Pan, Cai-Ping Tan, Zong-Wan Mao
Summary: The first specific inducer and tracker of ERLAD was reported and used to track the dynamic change of ER buds viscosity during ERLAD.
NATIONAL SCIENCE REVIEW
(2022)
Review
Immunology
Shiping Liu, Xiaoyu Fang, Ruiyao Zhu, Jing Zhang, Huijuan Wang, Jiaxi Lei, Chaoqun Wang, Lu Wang, Liying Zhan
Summary: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the main causes of morbidity and mortality in critically ill patients, and are typically treated with general supportive treatments. However, endoplasmic reticulum autophagy (ER-phagy) has been identified as a crucial process for maintaining cellular homeostasis and improving the internal environment. This review summarizes the definition, epidemiology, and pathophysiology of ALI/ARDS, as well as discusses the regulatory mechanisms and functions of ER-phagy in the context of immunity, inflammation, apoptosis, pathogen infection, and fibrosis. The potential role of ER-phagy in improving the prognosis of ALI/ARDS is also explored.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Zhiwei Sun, Doudou Liu, Bin Zeng, Qiting Zhao, Xiaoshuang Li, Hao Chen, Jianyu Wang, H. Rosie Xing
Summary: This study has revealed a new mechanism through which Sec23a inhibits the self-renewal of melanoma CSCs by inactivating ER-phagy, providing new insights into the regulatory network of CSC self-renewal.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Cell Biology
Ya'nan Qu, Rifeng Gao, Xiang Wei, Xiaolei Sun, Kun Yang, Huairui Shi, Yang Gao, Shiyu Hu, Yiwen Wang, Ji'e Yang, Aijun Sun, Feng Zhang, Junbo Ge
Summary: GSDMD regulates the interaction between FAM134B and LC3, promoting autophagy and inducing cardiomyocyte apoptosis, thus exacerbating doxorubicin-induced cardiotoxicity.
CELL DEATH & DISEASE
(2022)
Article
Plant Sciences
Jiaqi Sun, Weina Wang, Huanquan Zheng
Summary: This study reveals the involvement of RHD3 in the ER-phagy process under ER stress and the hyposensitivity of the rhd3 mutant to ER and salt stress. The increased association of RHD3 with ATG8e-marked autophagosomes and its breakdown under ER stress are demonstrated. The physical interaction between RHD3 and ATG8 is also enhanced under ER stress.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Rongjin Luo, Huaizhen Liang, Weifeng Zhang, Gaocai Li, Kangcheng Zhao, Wenbin Hua, Yu Song, Cao Yang
Summary: The study demonstrates that RETREG1-mediated ER-phagy plays a protective role in response to glucose deprivation treatment, with ER stress being suggested as an upstream event of ER-phagy. By modulating ER stress, ER-phagy can protect human nucleus pulposus cells against cell injury induced by GD treatment.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Food Science & Technology
Suzuka Uomoto, Keisuke Takesue, Saori Shimizu, Natsuno Maeda, Kanami Oshima, Emika Hara, Mio Kobayashi, Yasunori Takahashi, Makoto Shibutani, Toshinori Yoshida
Summary: We investigated the role of ER-phagy in NAFLD-related hepatocarcinogenesis in HFD-fed and/or PB-treated rats by clustering the expression levels of p62 and FAM134B in preneoplastic hepatic lesions. The results showed that PB administration increased clusters with high levels of p62, while HFD feeding increased clusters with high levels of both p62 and FAM134B. The combination of HFD feeding with PB counteracted each other's effects and the cluster composition resembled that of the control group.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mingzhu Yan, Zhi Wang, Tianji Xia, Suwei Jin, Yongguang Liu, Hongbo Hu, Qi Chang
Summary: This study investigated the role of ER-phagy in APA-induced liver injury (AILI) and found that delayed treatment with glycyrrhizin (GCM) can promote liver recovery by enhancing ER-phagy.
Review
Endocrinology & Metabolism
Ming Yang, Chongbin Liu, Na Jiang, Yan Liu, Shilu Luo, Chenrui Li, Hao Zhao, Yachun Han, Wei Chen, Li Li, Li Xiao, Lin Sun
Summary: The endoplasmic reticulum (ER) is an active organelle involved in various physiological processes. Recent studies have shown that dysfunction of the ER plays a role in the progression of kidney disease, particularly diabetic nephropathy (DN). This review discusses the function of the ER, the regulation of homeostasis through the unfolded protein response (UPR) and ER-phagy, as well as the impact of abnormal ER homeostasis in renal cells in DN. Additionally, potential therapeutic targets for DN related to maintaining ER homeostasis are also explored.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shatha Boukeileh, Odai Darawshi, Miriam Shmuel, Mohamed Mahameed, Thomas Wilhelm, Priya Dipta, Francesca Forno, Bellam Praveen, Michael Huber, Francesca Levi-Schaffer, Boaz Tirosh
Summary: This study found that activation of Fc epsilon RI leads to expansion of the endoplasmic reticulum (ER) and induction of the unfolded protein response (UPR) in mast cells. Inhibition of IRE1 alpha can suppress mast cell response to LPS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
M. R. Preetha Rani, P. Salin Raj, Anupama Nair, S. Ranjith, K. Rajankutty, K. G. Raghu
Summary: This study investigated the role of endoplasmic reticulum stress and its related pathways in diabetic cardiomyopathy, and found that endoplasmic reticulum stress plays a crucial role in the progression of the disease. Furthermore, chlorogenic acid was found to be beneficial against the pathological alterations caused by high glucose.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Plant Sciences
Yushi Yoshitake, Daiki Shinozaki, Kohki Yoshimoto
Summary: Inorganic phosphate is essential for plant growth, but it is often limited in soil. This study found that autophagy-deficient mutants showed early depletion of phosphate and severe growth defects under phosphate starvation. The main cargo of autophagy induced by early phosphate depletion was the endoplasmic reticulum (ER), indicating the involvement of ER-phagy in the response to early phosphate starvation for recycling phosphate. This ER-phagy was induced by ER stress and was suppressed by iron limitation and inhibition of lipid-reactive oxygen species accumulation. Interestingly, membrane lipid remodeling, a response to late phosphate starvation, was accelerated in mutants under early phosphate-depleted conditions. Overall, this study reveals the importance of ER stress-mediated ER-phagy in phosphate recycling during the early phase of phosphate starvation and its role in suppressing acceleration of the late phase.
Article
Cell Biology
Bin Wang, Jing Zhang, Xin Liu, Qingqing Chai, Xiaoran Lu, Xiaoyu Yao, Zhichang Yang, Liangliang Sun, Silas F. Johnson, Richard C. Schwartz, Yong-Hui Zheng
Summary: Zaire ebolavirus (EBOV) suppresses the expression of its structural glycoprotein (GP) through protein disulfide isomerases (PDIs), resulting in reduced pathogenicity. PDIs trigger misfolding of GP by targeting its cysteine residues and activate the unfolded protein response (UPR), leading to degradation of misfolded GP through ER-associated protein degradation (ERAD) and autophagy-lysosomal pathway. PDIs also have similar inhibitory activity on GP expression from other ebolavirus species.
Article
Agriculture, Dairy & Animal Science
Muhammad Rosyid Ridlo, Eui Hyun Kim, Eun Pyo Kim, Geon A. Kim
Summary: In this study, the application of miR-143 (mimics and inhibitors) to porcine parthenogenetically activated embryos showed that the miR-143 inhibitor can improve embryo development to the blastocyst stage, and is associated with increased activity of autophagy and ER-phagy as well as higher expression levels of genes related to embryo quality.
Article
Biochemistry & Molecular Biology
Andrea Gubas, Ivan Dikic
Summary: Autophagy is a highly conserved cellular process for degrading abnormal cellular components and foreign pathogens, which can be selective or nonselective. Autophagy receptors play a crucial role in linking and degrading cell components during autophagy, undergoing structural modifications to fulfill their function.
Article
Biochemistry & Molecular Biology
Benedikt Linder, Caterina Klein, Marina E. Hoffmann, Florian Bonn, Ivan Dikic, Donat Koegel
Summary: By regulating hallmarks of cancer, BAG3 plays oncogenic roles in various malignant diseases, and its knockdown enhances ciliogenesis and reduces cell migration.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Biology
Timurs Maculins, Erik Verschueren, Trent Hinkle, Meena Choi, Patrick Chang, Cecile Chalouni, Shilpa Rao, Youngsu Kwon, Junghyun Lim, Anand Kumar Katakam, Ryan C. Kunz, Brian K. Erickson, Ting Huang, Tsung-Heng Tsai, Olga Vitek, Mike Reichelt, Yasin Senbabaoglu, Brent Mckenzie, John R. Rohde, Ivan Dikic, Donald S. Kirkpatrick, Aditya Murthy
Summary: Defective autophagy associated with loss-of-function of the core autophagy gene Atg16l1 enhances innate immunity against intracellular bacteria such as Shigella flexneri by upregulating proteins involved in the antioxidant response to compensate for oxidative stress, thereby promoting bacterial clearance in myeloid cells.
Article
Biochemistry & Molecular Biology
Cristian Prieto-Garcia, Oliver Hartmann, Michaela Reissland, Thomas Fischer, Carina R. Maier, Mathias Rosenfeldt, Christina Schuelein-Voelk, Kevin Klann, Reinhard Kalb, Ivan Dikic, Christian Munch, Markus E. Diefenbacher
Summary: Squamous cell carcinomas (SCC) exhibit high mutational burden and platinum-based chemotherapy resistance, with increased Np63 expression associated with resistance; USP28 is recruited to sites of DNA damage and plays a regulatory role in DNA damage repair in SCC; Targeting the USP28- increment Np63 axis can overcome chemotherapy resistance in SCC.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Microbiology
Varnesh Tiku, Chun Kew, Eric M. Kofoed, Yutian Peng, Ivan Dikic, Man-Wah Tan
Summary: This study reveals that A. baumannii secretes an inflammatory bioactive lipid that activates multiple pro-inflammatory signaling pathways and induces cell death. This finding contributes to a better understanding of the immune mechanisms involved in A. baumannii infection.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Cell Biology
Ivan Dikic, Brenda A. Schulman
Summary: Recent studies have advanced our understanding of ubiquitylation, revealing unconventional ubiquitylation mechanisms used by pathogens to promote infection. Structural studies have shown that ubiquitin functions involve complex multivalent interactions that regulate transcription or protein degradation. Furthermore, these interactions can induce conformational changes and regulate protein degradation or transcription. These newly discovered mechanisms provide potential opportunities for innovative therapeutic interventions for diseases such as cancer and infectious diseases.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Daniela S. Krause, Ivan Dikic
Article
Cell Biology
Alexandra Hertel, Ludovico Martins Alves, Henrik Dutz, Georg Tascher, Florian Bonn, Manuel Kaulich, Ivan Dikic, Stefan Eimer, Florian Steinberg, Anja Bremm
Summary: This study revealed a mechanism of controlling mTORC1 activation cascade at lysosomes through USP32-regulated LAMTOR1 ubiquitination.
Article
Chemistry, Multidisciplinary
David A. Perez A. Berrocal, Thimmalapura M. Vishwanatha, Daniel Horn-Ghetko, J. Josephine Botsch, Laura A. Hehl, Sebastian Kostrhon, Mohit Misra, Ivan Dikic, Paul P. Geurink, Hans van Dam, Brenda A. Schulman, Monique P. C. Mulder
Summary: Protein post-translational modification with ubiquitin (Ub) is a versatile signal regulating cell biology, and diseases associated with impaired Ub modification present opportunities for novel targeted treatments. The final components of the ubiquitination cascade, E3 ligases, have potential as small molecule targets. UbSRhodol, an autoimmolative Ub-based probe, enables detection of changes in E3 transthiolation activity, making it suitable for high-throughput screening and identification of small molecules modulating E3 activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Editorial Material
Biochemistry & Molecular Biology
Angus I. Lamond, Ivan Dikic, Andre Nussenzweig, Christoph W. Mueller, Janet M. Thornton, Michael B. Yaffe
Article
Cell Biology
Anshu Bhattacharya, Rukmini Mukherjee, Santosh Kumar Kuncha, Melinda Elaine Brunstein, Rajeshwari Rathore, Stephan Junek, Christian Muench, Ivan Dikic
Summary: Acute lysosomal membrane damage reduces functional lysosomes, but they have a recovery potential independent of lysosomal biogenesis and remain unaffected in cells depleted in TFEB and TFE3. A lysosomal membrane regeneration pathway was discovered that depends on ATG8, LIMP2, TBC1D15, dynamin-2, kinesin-5B, and clathrin. LIMP2 acts as a lysophagy receptor, binding ATG8, which recruits TBC1D15 to damaged lysosomal membranes. TBC1D15 interacts with ATG8 proteins and stabilizes the autophagic lysosomal reformation machinery, promoting lysosomal tubule formation and dynamin-2-dependent scission.
NATURE CELL BIOLOGY
(2023)
Review
Immunology
Joao Mello-Vieira, Tobias Bopp, Ivan Dikic
Summary: Cell-autonomous immunity is the first line of defense for cells to recognize and eliminate invasive pathogens. Ubiquitination plays a crucial role in orchestrating immune signaling networks and stimulating the appropriate immune response. This review focuses on how ubiquitin connects pathogen sensing pathways to cellular responses and discusses therapeutic options for enhancing cell-autonomous immune responses.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Cell Biology
Alexis Gonzalez, Ivan Dikic
Meeting Abstract
Oncology
Alicia Haydo, Johanna Ertl, Jennifer Schmidt, Marina E. Hoffmann, Stephanie Hehlgans, Alisha Crider, Rajeshwari Rathore, Christel Herold-Mende, Ivan Dikic, Mingji Dai, Alexander Adibekian, Franz Roedel, Donat Koegel, Benedikt Linder
STRAHLENTHERAPIE UND ONKOLOGIE
(2023)