Review
Cell Biology
Vineet Choudhary, Roger Schneiter
Summary: Lipid droplets (LDs) store metabolic energy in the form of neutral lipids and originate from the endoplasmic reticulum (ER), maintaining contact with it to facilitate protein and lipid exchange. Proper formation of ER-LD junctions is crucial to prevent the formation of aberrant LDs, which can impact lipid homeostasis and lead to lipid storage diseases. The close contacts between LDs, peroxisomes, and mitochondria play a role in metabolic channeling of fatty acids, highlighting the importance of LD contact sites in lipid metabolism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Pascal F. Egea
Summary: Eukaryotic cells exhibit exquisite compartmentalization through membrane-bound organelles, with membrane contact sites (MCSs) crucial for non-vesicular lipid trafficking. The endoplasmic reticulum (ER) and mitochondria play key roles in phospholipid biosynthesis and distribution, while proteinaceous tethers at MCSs mediate lipid transfer. Understanding these mechanisms is essential for various cellular processes involving lipid exchange and homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ruyue He, Furong Liu, Hui Wang, Shuai Huang, Kai Xu, Conggang Zhang, Yinghui Liu, Haijia Yu
Summary: In this study, it was discovered that ORP9 and ORP10 form a binary complex through intermolecular coiled-coil domain interaction. The PH domains of ORP9 and ORP10 specifically interact with PI4P and play a critical role in TGN targeting and regulating PI4P levels. ORP9 and ORP10 complex accelerate the transfer of PI4P between membranes and their PH domains participate in membrane tethering, while the ORD domains are required for lipid transport. Depletion of ORP9 and ORP10 leads to increased vesicle transport to the plasma membrane.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Plant Sciences
Vedrana Markovic, Yvon Jaillais
Summary: Phosphatidylinositol 4-phosphate (PI4P) mainly accumulates at the plasma membrane in plant cells and plays a key role in maintaining its electrostatic properties, establishing membrane contacts between the endoplasmic reticulum and the plasma membrane, exocytosis, and signaling pathways.
Review
Plant Sciences
Pengwei Wang, Patrick Duckney, Erlin Gao, Patrick J. J. Hussey, Verena Kriechbaumer, Chengyang Li, Jingze Zang, Tong Zhang
Summary: Functional regulation and structural maintenance of organelles in plants are crucial for plant development, reproduction, and stress responses. Recent studies have identified proteins that regulate membrane connections in plants, providing insights into the mechanism and function of these connections. The endoplasmic reticulum plays a key role in linking different subcellular compartments in plants, and its membrane contact sites (MCS) and ER-plasma membrane contact sites (EPCS) have been extensively studied. However, plant MCS are different from those in other eukaryotic systems. In this article, we summarize the recent advances in understanding these essential links in plants and discuss their mechanisms and biological relevance.
Review
Biochemistry & Molecular Biology
Feng Lin, Junming Zheng, Yanhua Xie, Wen Jing, Qun Zhang, Wenhua Zhang
Summary: Eukaryotic cells are enclosed by membranes that act as hydrophobic barriers, and the accumulation of regulatory lipids in specific membranes plays a crucial role in plant stress responses.
JOURNAL OF GENETICS AND GENOMICS
(2022)
Article
Cell Biology
Yang Emma Li, Yichang Wang, Ximing Du, Tizhong Zhang, Hoi Yin Mak, Sarah E. Hancock, Holly McEwen, Elvis Pandzic, Renee M. Whan, Yvette Celine Aw, Ivan E. Lukmantara, Yiqiong Yuan, Xiuju Dong, Anthony Don, Nigel Turner, Shiqian Qi, Hongyuan Yang
Summary: TMEM41B and VMP1 are integral membrane proteins of the endoplasmic reticulum, regulating the formation of lipid droplets and lipoproteins, and playing a crucial role in viral infection. They act as phospholipid scramblases, affecting the cellular distribution of cholesterol and phosphatidylserine.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Cell Biology
Bailey Hewlett, Neha Pratap Singh, Christian Vannier, Thierry Galli
Summary: Membrane contact sites play crucial roles in cell differentiation, plasticity and maintenance, and dysfunction can lead to pathological conditions. Each membrane contact site displays a unique molecular signature, adapted to the functions of different organelles.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Editorial Material
Cell Biology
Ying Yang, Daniel J. Klionsky
Summary: This study reveals that under glucose starvation, AMPK activates ULK1 to regulate the phosphorylation of PIKFYVE, leading to increased formation of PtdIns5P-containing autophagosomes and upregulation of autophagy. This novel discovery not only expands our understanding of autophagy but also provides insights into potential therapeutic strategies for glucose-related disorders.
Editorial Material
Cell Biology
Tizhong Zhang, Yang E. Li, Yiqiong Yuan, Ximing Du, Yichang Wang, Xiuju Dong, Hongyuan Yang, Shiqian Qi
Summary: TMEM41B and VMP1, two endoplasmic reticulum-resident transmembrane proteins, play crucial roles in regulating the formation of lipid droplets, autophagy initiation, and viral infection by affecting cholesterol and phosphatidylserine distribution. Their scramblase activity is key to understanding their mechanism of action.
Article
Multidisciplinary Sciences
Hao Ye, Jiayang Gao, Zizhen Liang, Youshun Lin, Qianyi Yu, Shuxian Huang, Liwen Jiang
Summary: This study identifies and demonstrates the role of Arabidopsis oxysterol-binding protein-related protein 2A (ORP2A) in mediating ER-autophagosomal membrane contacts and autophagosome biogenesis. ORP2A interacts with VAMP-associated protein 27-1 and ATG8e to form membrane contact sites between the ER and autophagosomes. Knockdown of ORP2A leads to impaired autophagy levels and inhibited plant growth. Additionally, ORP2A binds multiple phospholipids and colocalizes with phosphatidylinositol 3-phosphate (PI3P).
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Amit S. Joshi
Summary: Peroxisomes are vital organelles in cells, generated and maintained through membrane contacts with other organelles, playing a crucial role in normal cellular function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Danai Maria Kotzampasi, Kyriaki Premeti, Alexandra Papafotika, Vasiliki Syropoulou, Savvas Christoforidis, Zoe Cournia, George Leondaritis
Summary: This article investigates the interplay between PI3Ka and PTEN in cellular signaling and membrane trafficking, discusses the impact of their structure and catalytic activity on signaling, and explores the potential for pharmacological targeting of these proteins.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Cell Biology
Aurora Gil-Hernandez, Miguel Arroyo-Campuzano, Arturo Simoni-Nieves, Cecilia Zazueta, Luis Enrique Gomez-Quiroz, Alejandro Silva-Palacios
Summary: Membrane contact sites (MCS) are defined as areas of proximity between heterologous or homologous membranes characterized by specific proteins, playing a crucial role in regulating physiological processes such as apoptosis, calcium, and lipid signaling. Recent studies have highlighted the significance of MCS in cancer cells, particularly in calcium and lipid signaling, as well as their role in tumor progression, which may have implications for cancer biology research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Michael D. Guile, Akash Jain, Kyle A. Anderson, Catherine F. Clarke
Summary: Coenzyme Q (CoQ) is a vital lipid that plays multiple cellular functions, including cellular respiration, antioxidant protection, redox homeostasis, and ferroptosis suppression. Deficiencies in CoQ can be ameliorated by high-dose supplementation, and understanding its uptake and transport can improve clinical use and deficiency treatment. This review summarizes the current knowledge of CoQ uptake and intracellular distribution in yeast, mammalian cell culture, rodent models, and organism level absorption. The literature suggests that CoQ uptake and distribution are complex processes involving the endomembrane system and newly identified lipid transporters, with impairment causing significant effects on metabolism and stress response. Furthermore, significant gaps in our understanding of CoQ distribution within the cell are identified, suggesting future research directions.
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
Gastroenterology & Hepatology
Mansi Arora, James M. Bogenberger, Amro M. Abdelrahman, Jennifer Yonkus, Roberto Alva-Ruiz, Jennifer L. Leiting, Xianfeng Chen, Pedro Luiz Serrano Uson, Chelsae R. Dumbauld, Alexander T. Baker, Scott Gamb, Jan B. Egan, Yumei Zhou, Bolni Marius Nagalo, Nathalie Meurice, Eeva-Liisa Eskelinen, Marcela A. Salomao, Heidi E. Kosiorek, Esteban Braggio, Michael T. Barrett, Kenneth H. Buetow, Mohamad B. Sonbol, Aaron S. Mansfield, Lewis R. Roberts, Tanios S. Bekaii-Saab, Daniel H. Ahn, Mark J. Truty, Mitesh J. Borad
Summary: The combination of gemcitabine/cisplatin and CDK4/6 inhibitors showed enhanced efficacy, reduced toxicity, and better survival in BTC models. Monotherapy with abemaciclib had modest efficacy due to autophagy-induced resistance, but triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Abemaciclib also potentiated sensitization to gemcitabine through reduction of ribonucleotide reductase catalytic subunit M1.
Article
Immunology
Iwona T. Myszor, Snaevar Sigurdsson, Alexia Ros Viktorsdottir, Birgitta Agerberth, Eeva-Liisa Eskelinen, Margret Helga Ogmundsdottir, Gudmundur H. Gudmundsson
Summary: This study found that APD HO53 induces autophagy through a complex mechanism involving multiple pathways and epigenetic events. The induction of autophagy is associated with activation of AMPK, nuclear translocation of TFEB, and changes in expression of autophagy-related genes.
JOURNAL OF INNATE IMMUNITY
(2022)
Article
Multidisciplinary Sciences
Tanja Buchacher, Anni Honkimaa, Tommi Valikangas, Niina Lietzen, M. Karoliina Hirvonen, Jutta E. Laiho, Amir-Babak Sioofy-Khojine, Eeva-Liisa Eskelinen, Heikki Hyoty, Laura L. Elo, Riitta Lahesmaa
Summary: Enteroviruses, especially group B coxsackieviruses (CVBs), have been linked to the development of type 1 diabetes. However, the mechanisms behind persistent enterovirus infection and beta cell autoimmunity are not fully understood. This study established a persistent infection model using two CVB1 strains in a human pancreatic cell line and observed changes in gene expression related to the pancreatic microenvironment, secretory pathway, and lysosomal biogenesis. The antiviral response pathways were also found to be differently activated by the two strains.
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
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
Cell Biology
A. R. Tornero-Ecija, M. A. Navas, S. Munoz-Braceras, O. Vincent, R. Escalante
Summary: VPS13A is a lipid transfer protein located at different membrane contact sites between organelles, and its mutations cause a rare neurodegenerative disease called chorea-acanthocytosis (ChAc). Depletion of VPS13A in HeLa cells leads to an accumulation of endosomal and lysosomal markers, indicating a defect in lysosomal degradation capacity and autophagic dysfunction. By generating a KO model using CRISPR/Cas9, the study found that inactivation of VPS13A impairs cell growth, leading to the optimization of the use of pool cells for comparative analysis of phenotypes. The results suggest that modulation of the autophagic and lysosomal pathway could be a therapeutic target in the treatment of ChAc.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Editorial Material
Cell Biology
Eric Chevet, Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Hesso Farhan
Article
Biology
Alba Tornero-Ecija, Antonia Zapata-del-Bano, Laura Anton-Esteban, Olivier Vincent, Ricardo Escalante
Summary: Human VPS13 proteins are involved in severe neurological diseases and play a crucial role in lipid transport at membrane contact sites. The identification of adaptors that regulate their subcellular localization is essential for understanding their function and role in disease. We found that the sorting nexin SNX5 interacts with VPS13A and mediates its association with endosomes, involving specific domains in both proteins.
LIFE SCIENCE ALLIANCE
(2023)
Review
Biochemistry & Molecular Biology
Eeva-Liisa Eskelinen
Summary: The generation of autophagosomes is a long-standing question in the field of autophagy. Recent studies using cryo-electron tomography and detailed analysis of image data have revealed new information on the membrane dynamics of autophagosome biogenesis, including the shape and dimensions of omegasomes, phagophores, and autophagosomes, and their relationships with surrounding organelles. An important prediction from these findings is that 60-80% of the autophagosome membrane area is obtained through direct lipid transfer or lipid synthesis. Cryo-electron tomography is expected to provide new directions for autophagy research in the future.
Editorial Material
Cell Biology
Eric Chevet, Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Hesso Farhan
Article
Biochemistry & Molecular Biology
Miranda Bueno-Arribas, Celia Cruz-Cuevas, Maria-Angeles Navas, Ricardo Escalante, Olivier Vincent
Summary: PROPPINs/WIPIs are beta-propeller proteins that participate in membrane remodelling processes. This study identified critical residues in Atg21 and Atg16 for protein-protein binding by using the RD2H method. The dimerization of the Atg16 coiled-coil domain is required for Atg21 binding, and the conserved residues in Atg21 and WIPI2 mediate ATG16L1 binding. These findings suggest that different autophagic proteins use different amino acids at the same position to interact with each other.
