Editorial Material
Cell Biology
Vikramjit Lahiri, Daniel J. Klionsky
Summary: Nguyen et al. discovered a previously unexplored role for mammalian ATG4s in mitophagy, involving the recruitment of ATG9A-containing vesicles. Their article highlights the use of a novel AI-directed analysis technique for FIB-SEM imaging to demonstrate the role of ATG4s in promoting phagophore growth and establishing phagophore-ER contacts.
Article
Cell Biology
Weijing Yao, Yixing Li, Yingcong Chen, Yuting Chen, Yu Xie, Miaojuan Ye, Ying Zhang, Xiangjun Chen, Xiaoyong Wu, Yuyao Feng, Zhi Hong, Yigang Wang, Wei Liu, Cong Yi
Summary: Atg11 is phosphorylated by Atg1, which induces slower electrophoretic mobility of Atg11 and regulates selective autophagy. Atg1 phosphorylates S949, S1057, and S1064 residues in the CC4 domain of Atg11. Mutating these residues impairs the cleavage of selective autophagy substrates and the binding of Atg11 to selective autophagy receptors. These findings reveal a previously unknown function of Atg1 in regulating selective autophagy through Atg11 phosphorylation.
Article
Cell Biology
Vikramjit Lahiri, Shree Padma Metur, Zehan Hu, Xinxin Song, Muriel Mari, Wayne D. Hawkins, Janakraj Bhattarai, Elizabeth Delorme-Axford, Fulvio Reggiori, Daolin Tang, Joern Dengjel, Daniel J. Klionsky
Summary: This study reveals that subtle changes in nutrient availability can have a significant impact on autophagy flux through unknown post-transcriptional regulatory mechanisms affecting the expression of key autophagy-inducing kinase. The identification of two novel post-transcriptional regulators further highlights the complexity of autophagy regulation.
Article
Biochemistry & Molecular Biology
Gemma G. Martinez-Garcia, Raul F. Perez, Alvaro F. Fernandez, Sylvere Durand, Guido Kroemer, Guillermo Marino
Summary: Autophagy is crucial for maintaining cellular and tissue homeostasis, and dysfunction can lead to various pathologies. The metabolic effects of systemic reduction of autophagy are tissue-dependent, with skeletal muscle and plasma showing the most pronounced alterations. This study sheds light on how impaired autophagy may impact the metabolism of different tissues in mammals.
Article
Cell Biology
Yuanyuan Zhou, Zhenkun Wang, Yijia Huang, Chujie Bai, Xianli Zhang, Mengdie Fang, Zhenyu Ju, Bo Liu
Summary: The biogenesis of autophagosomes is essential for macroautophagy to capture and degrade intracellular cargoes. ATG4B localizes to early autophagic membranes in an LC3B-dependent manner, and its activity controls the efficiency of autophagosome formation by impacting the membrane binding/dissociation of LC3B. ATG4 and LC3 play interdependent roles in the formation of autophagosomes.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2021)
Editorial Material
Cell Biology
Xinyu Gong, Lifeng Pan
Summary: The recruitment of ATG12-ATG5-ATG16L1 complex to phagophore, which is crucial in autophagosome formation, relies on the specific interaction between ATG16L1 and WIPI2. It has been found that ATG16L1 contains two distinct WIPI2-binding sites, WBS1 and the newly identified WBS2, and the binding mechanism between ATG16L1 WBS2 and WIPI2 is conserved across species. The integrity of these two WIPI2-binding sites in ATG16L1 is essential for normal autophagic flux.
Article
Cell Biology
Wenmei Wu, Kang Li, Sanyou Guo, Jing Xu, Qiuqin Ma, Shuyan Li, Xianying Xu, Zhijun Huang, Yangjin Zhong, Gianluca Tettamanti, Yang Cao, Sheng Li, Ling Tian
Summary: The study reveals that acetylation plays a crucial role in regulating the localization and function of components in the BmAtg8-PE ubiquitin-like system in Bombyx mori, affecting autophagy induction and inhibition.
CELL DEATH DISCOVERY
(2021)
Review
Physiology
Shengyuan Wang, Hongyan Li, Minghao Yuan, Haixia Fan, Zhiyou Cai
Summary: Adenosine monophosphate-activated protein kinase (AMPK) plays a significant role in maintaining cellular energy homeostasis and is linked with different stages of autophagy.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ting Huang, Gaoyue Jiang, Yabin Zhang, Yuqing Lei, Shiyan Liu, Huihui Li, Kefeng Lu
Summary: This study identifies Rpb9, a subunit of RNA polymerase II, as a crucial regulator of autophagy by upregulating ATG1 transcription. This finding is validated in mammalian cells, revealing an important regulatory mechanism of the autophagy process.
Review
Chemistry, Medicinal
Fan Xia, Peiqing Liu, Min Li
Summary: This paper summarizes the regulation of ATG4 activity, including factors such as micro-RNAs, posttranslational modifications, and small molecules. It also explores the roles of ATG4 in various diseases, such as cancer, neurodegeneration, microbial infection, and provides insight into potential therapeutic opportunities targeting ATG4 for future research and human health.
MEDICINAL RESEARCH REVIEWS
(2021)
Editorial Material
Cell Biology
Wenzhi Feng, Orlando Arguello-Miranda, Suhong Qian, Fei Wang
Summary: The coordination of autophagy activity during meiosis progression is regulated by the phosphatase Cdc14, which stimulates autophagy initiation and facilitates meiotic divisions.
Editorial Material
Cell Biology
Linfang Wang, Shiping Zhang, Shuanglong Yi, Margaret S. Ho
Summary: Research has shown that GAK/aux (cyclin-G-associated kinase/auxilin) is an important regulator of autophagy in glial cells. In the absence of GAK/aux, the number and size of autophagosomes and autophagosomal precursors increase, and the protein levels of components in the initiation and PtdIns3K complexes are upregulated. GAK/aux interacts with ULK1/Atg1 and inhibits autophagy activation by competing with ATG13 for binding to ULK1, and also regulates ULK1 trafficking. However, the lack of GAK/aux impairs autophagic flux and substrate degradation, indicating additional roles for GAK/aux. Overall, this study reveals a new regulator of autophagy initiation in glia and advances our understanding of how glial cells contribute to Parkinson's disease by eliminating pathological protein aggregates.
Article
Biochemistry & Molecular Biology
Alexandra Polyansky, Oren Shatz, Milana Fraiberg, Eyal Shimoni, Tali Dadosh, Muriel Mari, Fulvio M. Reggiori, Chao Qin, Xianlin Han, Zvulun Elazar
Summary: This study investigates the role of phosphatidylcholine (PC) in autophagy using yeast as a model organism. The results show that PC is important for autophagosome formation and that disruption of PC biosynthesis leads to changes in lipid composition and impaired autophagic flux.
Article
Cell Biology
Hong Huang, Qinqin Ouyang, Kunrong Mei, Ting Liu, Qiming Sun, Wei Liu, Rong Liu
Summary: This study reveals that both acetylation and phosphorylation modifications control the function of SCFD1 in autophagosome-lysosome fusion. KAT2B/PCAF catalyzes the acetylation of SCFD1, while SIRT4 deacetylates it. Additionally, AMPK-controlled phosphorylation disrupts the interaction between SCFD1 and KAT2B and inhibits SCFD1 acetylation. Furthermore, SCFD1 acetylation inhibits autophagic flux by blocking SNARE complex formation.
Article
Cell Biology
Wei Wan, Wei Liu
Summary: STING interacts directly with WIPI2 to recruit WIPI2 to STING-positive vesicles for LC3 lipidation and autophagosome formation. STING and PtdIns3P competitively bind to the FRRG motif of WIPI2, resulting in mutual inhibition between STING-induced and PtdIns3P-dependent autophagy. Additionally, the STING-WIPI2 interaction is essential for clearing cytoplasmic DNA and attenuating activated cGAS-STING signaling.
Review
Cell Biology
Yasmina Filali-Mouncef, Catherine Hunter, Federica Roccio, Stavroula Zagkou, Nicolas Dupont, Charlotte Primard, Tassula Proikas-Cezanne, Fulvio Reggiori
Summary: Autophagic pathways intersect with lipid homeostasis to provide energy and building blocks essential for liver functions. Disruption of lipophagy regulation in fatty liver diseases, especially nonalcoholic steatohepatitis (NASH), may contribute to the development of hepatocellular carcinomas. This review focuses on the role of macroautophagy and macrolipophagy in NASH, highlighting the impact of inappropriate lipophagy on various types of liver cells.
Review
Cell Biology
Mariya Licheva, Babu Raman, Claudine Kraft, Fulvio Reggiori
Summary: Post-translational modifications play a crucial role in diversifying and coordinating protein networks in eukaryotic cells, particularly in processes like autophagy where the balance of kinases and phosphatases is essential. Autophagy, a highly conserved self-degradation process, is vital for survival, stress adaptation, and maintaining cellular and organismal homeostasis. Studies have highlighted the significance of kinases and phosphatases in regulating autophagy, targeting core autophagy proteins, and the relevance of phosphorylation for the overall process.
Review
Cell Biology
Claudia Rio-Berge, Yingying Cong, Fulvio Reggiori
Summary: The cytoskeleton plays a crucial role in various physiological functions within the cell. Viruses can exploit the cytoskeleton by interacting with motor proteins to facilitate their own lifecycle. Understanding these interactions can provide insights into infection mechanisms and potential drug targets.
Article
Cell Biology
Ann De Maziere, Jan van der Beek, Suzanne van Dijk, Cecilia de Heus, Fulvio Reggiori, Masato Koike, Judith Klumperman
Summary: This study presents an optimized procedure for localizing endogenous LC3 at ultrastructural resolution. It provides researchers with a tool to study the canonical and non-canonical roles of LC3 in native conditions.
Article
Cell Biology
Prado Vargas Duarte, Ralph Hardenberg, Muriel Mari, Stefan Walter, Fulvio Reggiori, Florian Froehlich, Ayelen Gonzalez Montoro, Christian Ungermann
Summary: Lysosomes degrade macromolecules for cellular recycling and lysosome-related organelles mediate cell type-specific functions. Loss of the LYST protein leads to defects in lysosomes and lysosome-related organelles, causing Chediak-Higashi syndrome. The molecular function of LYST, however, remains largely unknown. In this study, the function of the yeast LYST homolog, Bph1, was investigated. Bph1 was found to be an endosomal protein and an effector of the minor Rab5 isoform Ypt52. Mutant cells lacking Bph1 showed lipidated Atg8 on their endosomes, which is normally sorted to the vacuole lumen via late endosomes. These findings contribute to our understanding of the role of LYST-related proteins and associated diseases.
JOURNAL OF CELL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Stephanie Kaeser-Pebernard, Christine Vionnet, Muriel Mari, Devanarayanan Siva Sankar, Zehan Hu, Carole Roubaty, Esther Martinez-Martinez, Huiyuan Zhao, Miguel Spuch-Calvar, Alke Petri-Fink, Gregor Rainer, Florian Steinberg, Fulvio Reggiori, Joern Dengjel
Summary: mTORC1, as a master regulator of cell growth, not only inhibits autophagic vesicle formation but also affects Golgi architecture and vesicle secretion by phosphorylating the scaffold protein SCYL1. This study reveals the multiple functions of mTORC1 at the subcellular level, which is important for understanding tumor cell proliferation and the pathogenesis of human genetic diseases.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Alexandra Polyansky, Oren Shatz, Milana Fraiberg, Eyal Shimoni, Tali Dadosh, Muriel Mari, Fulvio M. Reggiori, Chao Qin, Xianlin Han, Zvulun Elazar
Summary: This study investigates the role of phosphatidylcholine (PC) in autophagy using yeast as a model organism. The results show that PC is important for autophagosome formation and that disruption of PC biosynthesis leads to changes in lipid composition and impaired autophagic flux.
Review
Biochemistry & Molecular Biology
Mario Mauthe, Harm H. Kampinga, Mark S. Hipp, Fulvio Reggiori
Summary: Aggrephagy is the process of selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. Protein aggregates are polyubiquitinated and sequestered by autophagosomes. Soluble selective autophagy receptors (SARs) play a central role in aggrephagy by physically binding to ubiquitin and the autophagy machinery. Understanding the mechanism of aggrephagy can potentially lead to therapeutic strategies for preventing the buildup of potentially toxic protein aggregates.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Cell Biology
Sabrina Chumpen Ramirez, Ruben Gomez-Sanchez, Pauline Verlhac, Ralph Hardenberg, Eleonora Margheritis, Katia Cosentino, Fulvio Reggiori, Christian Ungermann
Summary: During autophagy, Atg9 plays a critical role in establishing membrane contact sites and promoting lipid transfer. However, a specific mutation in Atg9 can impair autophagy progression by blocking phagophore expansion.
Review
Cell Biology
Emma Zwilling, Fulvio Reggiori
Summary: This article summarizes the role of MCSs in autophagosome formation, with a focus on budding yeast and mammalian systems.
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
Henning Arlt, Babu Raman, Yasmina Filali-Mouncef, Yan Hu, Alexandre Leytens, Ralph Hardenberg, Rodrigo Guimaraes, Franziska Kriegenburg, Muriel Mari, Iwona I. Smaczynska-de Rooij, Kathryn R. Ayscough, Christian Ungermann, Joern Dengjel, Fulvio Reggiori
Summary: Autophagy is a crucial cellular process that maintains homeostasis by degrading cellular components. This study reveals that Vps1 mutants affect the subcellular distribution of Atg9 and impair autophagy. The findings provide new insights into the role of dynamins in Atg9 trafficking and their potential contribution to severe human pathologies associated with autophagy defects.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Hector Foronda, Yangxue Fu, Adriana Covarrubias-Pinto, Hartmut T. Bocker, Alexis Gonzalez, Eric Seemann, Patricia Franzka, Andrea Bock, Ramachandra M. M. Bhaskara, Lutz Liebmann, Marina E. E. Hoffmann, Istvan Katona, Nicole Koch, Joachim Weis, Ingo Kurth, Joseph G. G. Gleeson, Fulvio Reggiori, Gerhard Hummer, Michael M. M. Kessels, Britta Qualmann, Muriel Mari, Ivan Dikic, Christian A. A. Huebner
Summary: Membrane-shaping proteins containing reticulon homology domains are crucial for dynamic remodelling of the endoplasmic reticulum (ER). FAM134B is an example of such a protein, which mediates the degradation of ER sheets through a process called selective autophagy (ER-phagy) by binding to LC3 proteins. Mutations in FAM134B result in a neurodegenerative disorder in humans.
Review
Biochemistry & Molecular Biology
Claudine Kraft, Fulvio Reggiori
Summary: This review discusses three membrane remodeling steps in autophagy: closure of phagophores, maturation of autophagosomes, and fusion with vacuoles/lysosomes. The focus is on the role and contribution of Saccharomyces cerevisiae in studying molecular events in autophagy.
Article
Immunology
Chairi Misrielal, Astrid M. Alsema, Marion H. C. Wijering, Anneke Miedema, Mario Mauthe, Fulvio Reggiori, Bart J. L. Eggen
Summary: Autophagy plays a crucial role in different stages of multiple sclerosis (MS) pathology, with decreased expression of autophagy-related genes observed in the acute phase of MS and postmortem brain tissues. The negative regulation of autophagy in MS may be mediated through persistent activation of the mTORC1 pathway, affecting CNS homeostasis and neuroinflammation in MS.
BRAIN, BEHAVIOR, & IMMUNITY - HEALTH
(2022)
