Editorial Material
Cell Biology
Paulina Strzyz
Summary: The wetting process, where a liquid comes into contact with a surface, plays a crucial role in the interactions between phase-separated droplets and autophagic membranes, as reported by Agudo-Canalejo et al. in Nature.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
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
Cell Biology
Taryn J. J. Olivas, Yumei Wu, Shenliang Yu, Lin Luan, Peter Choi, Emily D. D. Guinn, Shanta Nag, Pietro V. V. De Camilli, Kallol Gupta, Thomas J. J. Melia
Summary: ATG9 vesicles serve as the membrane seed for mammalian autophagosomes, as shown by Olivas et al. using nanodisc technology. The integration of ATG9 with expanding autophagosome membranes demonstrates the importance of lipid transfer in autophagosome expansion. This work provides significant insights into the model of autophagosome formation and expands our understanding of the cellular process of autophagy.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Cell Biology
Milana Fraiberg, Bat-Chen Tamim-Yecheskel, Kamilya Kokabi, Nemanja Subic, Gali Heimer, Franziska Eck, Karsten Nalbach, Christian Behrends, Bruria Ben-Zeev, Oren Shatz, Zvulun Elazar
Summary: TECPR2, a large, multi-domain protein, plays a crucial role in lysosomal targeting of autophagosomes by associating with Atg8-family proteins on autophagosomes and VAMP8 on lysosomes. This protein is linked to spastic paraplegia type 49 (SPG49), where impaired autophagic flux is observed in patient fibroblasts.
Article
Multidisciplinary Sciences
Gayatri Saberwal
Summary: Registries are essential for boosting trial enrollment, reducing bias in published literature, and addressing a wide range of questions. It is crucial to establish and maintain registries, ensure accurate and comprehensive trial records, and support research on registry data.
Editorial Material
Cell Biology
Ikuko Koyama-Honda, Noboru Mizushima
Summary: This article summarizes the current understanding of the mechanism of STX17 translocation and the duration of its stay during the fusion process between autophagosomes and lysosomes, and discusses unresolved questions.
Article
Biochemistry & Molecular Biology
Suresh Kumar, Ruheena Javed, Michal Mudd, Sandeep Pallikkuth, Keith A. Lidke, Ashish Jain, Karthikeyan Tangavelou, Sigurdur Runar Gudmundsson, Chunyan Ye, Tor Erik Rusten, Jan Haug Anonsen, Alf Hakon Lystad, Aurore Claude-Taupin, Anne Simonsen, Michelle Salemi, Brett Phinney, Jing Li, Lian-Wang Guo, Steven B. Bradfute, Graham S. Timmins, Eeva-Liisa Eskelinen, Vojo Deretic
Summary: The biogenesis of mammalian autophagosomes involves the fusion of FIP200 vesicles with endosomally derived ATG16L1 membranes, forming a hybrid pre-autophagosomal structure called HyPAS. Pharmacological agents can modulate HyPAS formation, while it is inhibited by SARS-CoV-2 infection.
Article
Biochemistry & Molecular Biology
Ewelina Bik, Lukasz Mateuszuk, Jagoda Orleanska, Malgorzata Baranska, Stefan Chlopicki, Katarzyna Majzner
Summary: The antimalarial drug Chloroquine (CQ) was found to not be toxic to endothelial cells at concentrations of 1-30 μM and did not induce inflammation. However, it did lead to increased staining intensity of neutral lipids, lysosomotropism, and autophagy inhibition. This indicates alterations in lipid composition of endothelial cells upon exposure to CQ.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Kevin M. Keary III, Qin-Hua Gu, Jiji Chen, Zheng Li
Summary: The mechanism of long-term depression (LTD) is extensively studied in Schaffer collateral (SC) synapses, and inhibition of autophagy is identified as a key factor. Here, it is demonstrated that the temporoammonic pathway (TAP) and SC synapses have a shared LTD mechanism reliant on NMDA receptors, caspase-3, and autophagy inhibition. The distribution of autophagosomes in dendrites and distinct LTD induction at SC and TAP synapses suggest a model where autophagosomes gate LTD inducibility.
Article
Biochemistry & Molecular Biology
Jose L. Nieto-Torres, Sean-Luc Shanahan, Romain Chassefeyre, Tai Chaiamarit, Sviatlana Zaretski, Sara Landeras-Bueno, Adriaan Verhelle, Sandra E. Encalada, Malene Hansen
Summary: Autophagy is a conserved cellular process that promotes homeostasis by degrading cytosolic components. The ATG8 protein family interacts with FYCO1 to regulate the directional transport of autophagosomes.
Article
Cell Biology
Qixin Chen, Mingang Hao, Lei Wang, Linsen Li, Yang Chen, Xintian Shao, Zhiqi Tian, Richard A. Pfuetzner, Qing Zhong, Axel T. Brunger, Jun-Lin Guan, Jiajie Diao
Summary: The study revealed that lysosomes cluster around autophagosomes upon stimulation, setting the stage for membrane fusion, with the SNARE protein VAMP8 playing a crucial role in this prefusion state. Phosphorylation of VAMP8 was found to reduce spontaneous fusion under normal conditions while preassembling multiple lysosomes to increase fusion probability upon stimulation, impacting autophagosome maturation and chemotherapy drug resistance.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Yabin Zhang, Hao Sun, Rongjuan Pei, Binli Mao, Zhenyu Zhao, Huihui Li, Yong Lin, Kefeng Lu
Summary: The study identified that ORF3a protein of SARS-CoV-2 inhibits autophagic flux by blocking fusion of autophagosomes with lysosomes. This mechanism helps the virus evade degradation, and further research may lead to strategies targeting autophagy to combat the spread of SARS-CoV-2.
Article
Cell Biology
Anna Hilverling, Eva M. Szegoe, Elisabeth Dinter, Diana Cozma, Theodora Saridaki, Bjoern H. Falkenburger
Summary: The maturation of autophagosomes includes fusion with lysosomes and acidification. It was observed that neutral autophagosomes are located more frequently in the cell center, while acidic autophagosomes are more commonly found in the cell periphery. Acidic autophagosomes are transported towards the cell periphery more often, indicating acidification occurs in the cell center prior to transport to the periphery.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Genetics & Heredity
Zulin Wu, Haiqian Xu, Pei Wang, Ling Liu, Juan Cai, Yun Chen, Xiaomin Zhao, Xia You, Junze Liu, Xiangrui Guo, Tingting Xie, Jiajie Feng, Fan Zhou, Rui Li, Zhiping Xie, Yanhong Xue, Chuanhai Fu, Yongheng Liang
Summary: This study demonstrates that unclosed double-membrane autophagosomes can enter vacuoles after prolonged autophagy induction, potentially serving as a survival strategy. This finding provides a possible therapeutic strategy for diseases where autophagosome closure is impaired.