Article
Multidisciplinary Sciences
Anna Bieber, Cristina Capitanio, Philipp S. Erdmann, Fabian Fiedler, Florian Beck, Chia-Wei Lee, Delong Li, Gerhard Hummer, Brenda A. Schulman, Wolfgang Baumeister, Florian Wilfling
Summary: By combining different research methods, we directly revealed the structural progression of autophagosome biogenesis and organelle interactome within yeast cells. These findings have important implications for understanding the contribution of different membrane sources during autophagy and the forces shaping and driving phagophores.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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.
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.
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
Wayne D. Hawkins, Daniel J. Klionsky
Summary: Autophagy proteins often have multiple roles, not only in the process of autophagy but also potentially in other cellular processes.
Article
Biochemistry & Molecular Biology
Valeria Manganelli, Antonella Capozzi, Serena Recalchi, Gloria Riitano, Vincenzo Mattei, Agostina Longo, Roberta Misasi, Tina Garofalo, Maurizio Sorice
Summary: This study investigated the presence of cardiolipin (CL) within mitochondria-associated membranes (MAMs) following autophagic stimulus, and the potential role of CL-enriched raft-like microdomains as a signaling platform in autophagosome formation. The findings indicate that CL accumulates in MAM fractions after autophagic stimulation, where it interacts with proteins such as MFN2 and CANX, contributing to the multimolecular complex involved in autophagosome formation. This suggests that CL may have structural and functional implications in the pathophysiology of neurodegenerative diseases.
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.
Review
Cell Biology
Wenyan Jiang, Xuechai Chen, Cuicui Ji, Wenting Zhang, Jianing Song, Jie Li, Juan Wang
Summary: This review focuses on the closure of the isolation membrane to form the sealed autophagosome in autophagy, which is regulated by various proteins and molecules. Further research is needed to address remaining key questions in this process.
Article
Cell Biology
He-Yen Chou, Yi-Tang Lee, Yuchieh Jay Lin, Jung-Kun Wen, Wen-Hsin Peng, Pei-Lien Hsieh, Shu-Yu Lin, Chin-Chun Hung, Guang-Chao Chen
Summary: Macroautophagy/autophagy is an evolutionarily conserved intracellular pathway for the degradation of cytoplasmic materials. PTPN9 plays a crucial role in regulating the biogenesis of autophagosomes by modulating the phosphorylation status of VTI1B. The study highlights the importance of PTPN9 in the fusion of ATG16L1(+) autophagosome precursors and autophagosome formation.
Editorial Material
Cell Biology
Daniel J. Klionsky
Summary: The author has noticed a surprising number of papers with incorrect representations of the morphological intermediates of autophagy. This similarity in errors is not due to a deliberate agreement among researchers.
Editorial Material
Cell Biology
Hao Ye, Jiayang Gao, Liwen Jiang
Summary: A plant-specific protein complex has been identified, consisting of AT4G22540/OSBP2A/ORP2A, AT3G60600/VAP27-1, and AT2G45170/ATG8e, that mediates the contact between the endoplasmic reticulum (ER) and autophagosome membranes in plants. Knockdown of ORP2A affects autophagosome formation and seedling development, leading to the accumulation of the macroautophagic/autophagic core machinery and PtdIns3P in enlarged ER membranes. This study reveals the molecular architecture and functions of a distinct plant ER-autophagosome membrane contact site in regulating autophagosome formation through lipid redistribution.
Article
Immunology
Ainhoa Plaza-Zabala, Virginia Sierra-Torre, Amanda Sierra
Summary: Autophagy is a critical cellular process that helps cells clear debris and maintain innate immune function. Understanding autophagic flux is important for studying the stages of autophagy. To dissect the regulation and impact of autophagy, systematic analysis of both autophagosome formation and degradation stages is necessary.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Alba Tornero-Ecija, Luis-Carlos Tabara, Miranda Bueno-Arribas, Laura Anton-Esteban, Cristina Navarro-Gomez, Irene Sanchez, Olivier Vincent, Ricardo Escalante
Summary: PROPPINs are conserved PtdIns3P-binding proteins essential for autophagosome biogenesis, with mutations in WDR45/WIPI4 leading to the neurodegenerative disorder BPAN. Functional characterization in Dictyostelium discoideum reveals that the lack of Wdr45l significantly impairs autophagy, while Atg18 only causes subtle defects in autolysosome maturation. Mutants for Vmp1 and Wdr45l show similar phenotypes, including growth impairment in axenic medium and local enrichment of PtdIns3P. Additional mutation of the upstream regulator Atg1 can prevent altered PtdIns3P localization and restore axenic growth and reduce ER stress in both mutants.
Article
Materials Science, Multidisciplinary
Fatma Seden Tekin, P. Zeynep Culfaz-Emecen
Summary: The effects of three different solvent systems on the preparation of cellulose acetate membranes by phase inversion were investigated. Acetone as cosolvent resulted in an asymmetric membrane morphology, while acetic acid led to a loose, almost isotropic structure. The phase inversion rate was significantly lower when acetic acid was used as cosolvent, mainly due to its high viscosity.
ACS APPLIED POLYMER MATERIALS
(2023)
Article
Biotechnology & Applied Microbiology
Hsien-Shu Lin, Tung-Wu Lu, Jia-Da Li, Pei-An Lee, Yunn-Jy Chen
Summary: Knowledge of mandibular growth and development is crucial for diagnosing malformations and intervening early. This study utilized cone-beam computerized tomography to measure the 3D continuous growth of mandibles in miniature pigs. A new non-linear, time-dependent osteometric modeling approach was developed to analyze the morphological changes of the mandibles over a 12-month period. The results revealed non-linear patterns and rates of morphological changes in different regions of the mandible, providing valuable insights for future studies on mandibular growth in other animals.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jaime Agudo-Canalejo, Sebastian W. Schultz, Haruka Chino, Simona M. Migliano, Chieko Saito, Ikuko Koyama-Honda, Harald Stenmark, Andreas Brech, Alexander I. May, Noboru Mizushima, Roland L. Knorr
Summary: This study explores how autophagosomes sequester droplets containing p62 protein in cells and demonstrates the formation of double-membrane, autophagosome-like vesicles on protein-free droplets through partial wetting in vitro. A minimal physical model shows that droplet surface tension supports the formation of membrane sheets. The interaction between the material properties of droplets and membrane sheets elucidates the mechanisms underlying droplet autophagy.
Editorial Material
Cell Biology
Hideaki Morishita, Yuki Kanda, Noboru Mizushima
Summary: Macroautophagy plays a crucial role in the maturation of lamellar bodies, by fusing with immature lamellar bodies to increase their size and lipid contents. This function is essential for respiration after birth in mice and for maintaining buoyancy in zebrafish.
Editorial Material
Cell Biology
Sebastian W. Schultz, Jaime Agudo-Canalejo, Haruka Chino, Simona M. Migliano, Chieko Saito, Ikuko Koyama-Honda, Harald Stenmark, Andreas Brech, Noboru Mizushima, Roland L. Knorr, Alexander I. May
Summary: The wetting interactions between autophagic membranes and phase-separated droplets play a crucial role in determining the structure and fate of forming autophagosomes.
Editorial Material
Cell Biology
Willa Wen-You Yim, Noboru Mizushima
Summary: The study reveals that the SARS-CoV-2 protein ORF3a disrupts autophagy by interfering with the fusion between autophagosomes and lysosomes, through dysregulation of the HOPS complex.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Kaito Mimura, Jun-Ichi Sakamaki, Hideaki Morishita, Masahito Kawazu, Hiroyuki Mano, Noboru Mizushima
Summary: Autophagy is a process that degrades cytoplasmic material in lysosomes and undergoes dynamic regulation in response to cellular stress. A genome-wide CRISPR screen identified a component of the de novo purine synthesis pathway as a negative regulator of autophagy. These findings suggest a potential role for nucleotide metabolism in autophagy regulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Willa Wen-You Yim, Yoshitaka Kurikawa, Noboru Mizushima
Summary: Since the 1950s, the field of autophagy research has experienced exponential growth in publications, providing a wealth of information for researchers but also posing challenges for newcomers. The publication trend in the autophagy field can be separated into three phases, with the recent rapid increase likely driven by highly cited research papers from previous phases, leading to a wider variety of research topics, especially those related to diseases and modulating autophagy.
Review
Biochemistry & Molecular Biology
Yutaro Hama, Hideaki Morishita, Noboru Mizushima
Summary: The endoplasmic reticulum is essential for the biogenesis of various organelles and lipid-containing structures. Recent studies have shown that VMP1 and TMEM41B, two ER membrane proteins, play important roles in the formation of ER-derived structures and lipid scrambling activity.
Article
Cell Biology
Sidi Zhang, Euki Yazaki, Hirokazu Sakamoto, Hayashi Yamamoto, Noboru Mizushima
Summary: The ATG ubiquitin-like conjugation systems, ATG12 and ATG8, play important roles in macroautophagy. This study constructs a transcriptome database and identifies ATG conjugation system components in 94 eukaryotic species. It finds that functional diversification of these systems is more common than previously thought.
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
Haruka Chino, Akinori Yamasaki, Koji L. Ode, Hiroki R. Ueda, Nobuo N. Noda, Noboru Mizushima
Summary: This study reveals the critical role of LIR phosphorylation in the interaction, localization, and initiation of autophagy of the ER-phagy receptor TEX264 with ATG8. Structural analysis shows that phosphorylation increases binding affinity by generating multiple hydrogen bonds with ATG8, which cannot be mimicked by acidic residues. This finding highlights the importance of LIR phosphorylation in LIR-ATG8 interactions.
Article
Biochemistry & Molecular Biology
Willa Wen-You Yim, Hayashi Yamamoto, Noboru Mizushima
Summary: Damaged lysosomes can be repaired by the calcium release-dependent recruitment of the ESCRT machinery. However, the involvement of annexins in this process has not been fully understood. This study shows that ANXA1 and ANXA2 are important for the repair of damaged lysosomes, and their recruitment is calcium-dependent and independent of the ESCRT mechanism.
Article
Cell Biology
Tadayuki Komori, Tomoki Kuwahara, Tetta Fujimoto, Maria Sakurai, Ikuko Koyama-Honda, Mitsunori Fukuda, Takeshi Iwatsubo
Summary: Recent studies have identified Rab29 as a Rab protein phosphorylated by LRRK2 and found that it is also phosphorylated under lysosomal overload stress. The phosphorylation site is Ser185 and this phosphorylation is involved in counteracting lysosomal enlargement. PKCα and PKCδ are involved in this phosphorylation and control the lysosomal localization of Rab29.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Satoru Takahashi, Chieko Saito, Ikuko Koyama-Honda, Noboru Mizushima
Summary: This study investigated the relationships between organelles and phagophores, autophagosomes, and autolysosomes during macroautophagy using three-dimensional correlative light and electron microscopy. The findings suggest that most autophagosomes remain associated with the endoplasmic reticulum (ER) even after closure and fusion with lysosomes, and phagophores often form near other autophagic structures, potentially serving as hot spots for autophagosome formation.
CELL STRUCTURE AND FUNCTION
(2022)
