Article
Biochemistry & Molecular Biology
Thibault Courtellemont, Maria Giovanna De Leo, Navin Gopaldass, Andreas Mayer
Summary: Endo-lysosomal compartments exchange proteins through different processes, including fusion, fission, and endosomal transport carriers. The membrane fission events that occur during these processes are not well understood. This study identifies the CROP complex as a factor that plays a role in membrane fission. The CROP complex consists of members from two protein families and enhances the membrane fission activity of a specific protein. Disrupting the CROP complex prevents fragmentation of lysosome-like structures in yeast and impairs cargo export in mammalian endosomes.
Article
Chemistry, Medicinal
Feng Wang, Shan Li, Kai-Wen Cheng, William M. Rosencrans, Tsui-Fen Chou
Summary: The diverse modes of action of small molecule inhibitors provide versatile tools for research and therapeutics. This article focuses on two classes of inhibitors for the p97 ATPase: ATP competitive and allosteric. It shows that the allosteric p97 inhibitor UPCDC-30245 can alter autophagic pathways by increasing the lipidated form of LC3-II, and it blocks endo-lysosomal degradation by inhibiting early endosome formation and reducing lysosome acidity.
Article
Environmental Sciences
Zeyu Hu, Wanjing Xu, Jingjing Zhang, Yanling Tang, Hengrui Xing, Panpan Xu, Yue Ma, Qiang Niu
Summary: Excessive fluoride exposure impairs lysosomal biogenesis and autophagic degradation in the liver, leading to apoptosis. Transcription factor E3 (TFE3) plays a crucial role in regulating hepatocyte lysosomal biogenesis. Inhibition of TFE3 nuclear translocation by fluoride exposure results in compromised lysosomal function and impaired autophagic degradation, which can be restored by mTOR inhibitors rapamycin and Ad-TFE3. Therefore, TFE3 may be a potential therapeutic target for fluoride-induced hepatotoxicity.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Biochemistry & Molecular Biology
Katherine R. Balka, Rajan Venkatraman, Tahnee L. Saunders, Angus Shoppee, Ee Shan Pang, Zoe Magill, Jihane Homman-Ludiye, Cheng Huang, Rachael M. Lane, Harrison M. York, Peck Tan, Ralf B. Schittenhelm, Senthil Arumugam, Benjamin T. Kile, Meredith O'Keeffe, Dominic De Nardo
Summary: cGAS-STING signalling is initiated by detecting foreign or mislocalised DNA within the cytosol, leading to the production of interferons and inflammatory cytokines. STING is degraded within lysosomes, but the mechanisms controlling its delivery are poorly understood. In this study, the researchers used proteomics and microscopy to identify that the ESCRT pathway detects ubiquitinated STING on vesicles, facilitating its degradation in macrophages. Disruption of the ESCRT pathway enhances STING signalling and cytokine production, revealing a mechanism for effective termination of the pathway.
Article
Cell Biology
Valeria Coppola, Ilaria Marino, Uwe Warnken, Mario Falchi, Luca Pasquini, Mauro Biffoni, Ruggero De Maria, Tobias Longin Haas
Summary: We have identified FYCO1 as a protein that promotes the transport of autophagic and endosomal vesicles. It interacts with activated CASP8 and its loss leads to increased sensitivity of cells to apoptosis and impaired transport of TNFRSF10B/TRAIL-R2/DR5.
Review
Biology
Marton Molnar, Armin Soth, Zsofia Simon-Vecsei
Summary: This review summarizes recent scientific advances in the understanding of integrin trafficking in the endo-lysosomal system. It provides an overview of the internalization and recycling pathways of integrins, as well as the potential mechanisms of lysosomal degradation. The regulation of integrin internalization and recycling is a complex process that plays a critical role in cellular adhesion and migration. Dysregulation of this process can contribute to tumorigenesis and metastasis. Therefore, studying integrins in the endo-lysosomal system is of great importance, as it may lead to the identification of potential therapeutic targets and further insights into integrin signaling and adhesion-related processes.
Article
Cell Biology
Yves Pacheco, Dominique Valeyre, Thomas El Jammal, Maxime Vallee, Fabien Chevalier, Jerome Lamartine, Dominique Sigaudo-Roussel, Bernard Verrier, Dominique Israel-Biet, Nathalie Freymond, Vincent Cottin, Alain Calender
Summary: Sarcoidosis is a multisystem disease primarily affecting the lungs, with genetic predisposition being linked to mTOR-related pathways and autophagy regulation. Research suggests that genetic defects associated with sarcoidosis may increase the risk of severe SARS-CoV2 infection, with a focus on autophagy and mitophagy processes.
Review
Biochemistry & Molecular Biology
Xiaochen Xie, Ye Zhang, Zhuo Wang, Shanshan Wang, Xiaoyou Jiang, Hongyan Cui, Tingting Zhou, Zheng He, Hao Feng, Qiqiang Guo, Xiaoyu Song, Liu Cao
Summary: ROS, initially considered pathological, are now recognized as signaling intermediates that promote cellular adaptation to stress through autophagy regulation. ATM protein, activated by ROS, is involved in autophagy regulation, maintaining genome stability and triggering cytoplasmic autophagy as a ROS sensor.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Environmental Sciences
Yuan Liu, Yaxin Yao, Wenjing Tao, Feng Liu, Songbai Yang, Ayong Zhao, Dan Song, Xiangchen Li
Summary: This study investigated the role of CoQ10 in alleviating BPA-induced cell damage, demonstrating that CoQ10 effectively restored abnormalities caused by BPA, reduced apoptosis and ROS levels, improved mitochondrial membrane potential, and enhanced lysosome function and autophagy flux.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Review
Physiology
Fulvio Reggiori, Maurizio Molinari
Summary: ER-phagy is the process of degrading portions of the endoplasmic reticulum (ER) within lysosomes or vacuoles. It plays a role in recycling cytoplasmic material and organelles, regulating ER size and activity, and removing potentially cytotoxic material. Dysfunctional ER-phagy is associated with specific human diseases and can be targeted by pathogens.
PHYSIOLOGICAL REVIEWS
(2022)
Article
Chemistry, Medicinal
Junping Pei, Guan Wang, Lu Feng, Jifa Zhang, Tingting Jiang, Qiu Sun, Liang Ouyang
Summary: This article discusses strategies targeting lysosomal pathways and lysosome-based degradation techniques, as well as the advantages and challenges of lysosome-based degrading drugs. These tools can directly regulate protein levels in vivo and provide new strategies for treating diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Pengzhe Han, Shaojian Mo, Zhengwang Wang, Jiale Xu, Xifeng Fu, Yanzhang Tian
Summary: UXT, a widely expressed transcript, regulates cell death, cell metabolism, immune homeostasis, and neurodegenerative diseases through various mechanisms.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell Biology
Qin Xia, Hanfei Zheng, Yang Li, Wanting Xu, Chengwei Wu, Jiachen Xu, Shanhu Li, Lingqiang Zhang, Lei Dong
Summary: This study reveals that the autophagy regulator SMURF1 controls the nuclear translocation of TFEB, leading to the activation of lysosomal biogenesis. SMURF1 interacts with LGALS3 and PPP3CB to form a complex that stabilizes TFEB and promotes its activity. SMURF1 also controls the phosphatase activity of PPP3CB by promoting the dissociation of its inhibitory domain.
Article
Cell Biology
Chenchen Pan, Frank Winkler
Summary: This article reviews recent advances in understanding the interactions between cancer and the nervous system, and how this knowledge can be applied to improve cancer therapies. It highlights the importance of cancer neuroscience research and provides a roadmap for future studies.
NATURE CELL BIOLOGY
(2022)
Review
Cell Biology
Shin Hye Noh, Ye Jin Kim, Min Goo Lee
Summary: This article summarizes the multiple pathways involved in the secretion of cellular proteins and focuses on the unconventional protein secretion (UPS) pathways related to autophagy. By describing and comparing different features, the role and mechanisms of autophagy in the transport of secretory cargos, including leaderless soluble proteins and Golgi-bypassing transmembrane proteins, are revealed.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Clemens Alexander Boecker, Mara A. Olenick, Elizabeth R. Gallagher, Michael E. Ward, Erika L. F. Holzbaur
Article
Multidisciplinary Sciences
Andrew S. Moore, Stephen M. Coscia, Cory L. Simpson, Fabian E. Ortega, Eric C. Wait, John M. Heddleston, Jeffrey J. Nirschl, Christopher J. Obara, Pedro Guedes-Dias, C. Alexander Boecker, Teng-Leong Chew, Julie A. Theriot, Jennifer Lippincott-Schwartz, Erika L. F. Holzbaur
Summary: Actin assemblies play important roles in mitochondrial organization and inheritance during mitosis, ensuring equal segregation of mitochondrial mass at cytokinesis. Actin filaments on the surface of mitochondria form comet tails, promoting randomly directed bursts of movement to randomize inheritance of healthy and damaged mitochondria between daughter cells in symmetric cell division.
Article
Biochemistry & Molecular Biology
C. Alexander Boecker, Juliet Goldsmith, Dan Dou, Gregory G. Cajka, Erika L. F. Holzbaur
Summary: Mutations in the LRRK2 gene associated with Parkinson's disease lead to defects in autophagosome transport, impairing effective degradation of autophagosomal cargo in neurons.
Editorial Material
Cell Biology
C. Alexander Boecker, Erika L. F. Holzbaur
Summary: The hyperactivation of LRRK2 kinase activity is linked to defective axonal autophagosome transport in neurons, particularly in the context of Parkinson's disease. This disruption is caused by the recruitment of SPAG9/JIP4 and subsequent abnormal activation of kinesin-1, leading to impaired autophagosome maturation and degradation. Overall, these findings further establish the significance of defective autophagy in the pathogenesis of PD.
Article
Biology
Lisa M. Strong, Chunmei Chang, Julia F. Riley, C. Alexander Boecker, Thomas G. Flower, Cosmo Z. Buffalo, Xuefeng Ren, Andrea K. H. Stavoe, Erika L. F. Holzbaur, James H. Hurley
Summary: The study elucidates the recruitment mechanism of ATG12-5-16L1 on the autophagosomal membrane through the binding of ATG16L1 with WIPI2d, providing a framework for understanding the regulatory node connecting the initiation of autophagy.
Review
Biochemistry & Molecular Biology
C. Alexander Boecker
Summary: This review summarizes the role of LRRK2 in intracellular organelle dynamics, focusing on its effects on microtubule function, mitochondrial dynamics, the autophagy-lysosomal pathway, and synaptic vesicle trafficking. It highlights our current understanding of how intracellular dynamics are altered upon pathogenic LRRK2 hyperactivation.
JOURNAL OF MOLECULAR BIOLOGY
(2023)