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Angelina S Gross, Andreas Zimmermann, Tobias Pendl, Sabrina Schroeder, Hannes Schoenlechner, Oskar Knittelfelder, Laura Lamplmayr, Ana Santiso, Andreas Aufschnaiter, Daniel Waltenstorfer, Sandra Ortonobes Lara, Sarah Stryeck, Christina Kast, Christoph Ruckenstuhl, Sebastian J Hofer, Birgit Michelitsch, Martina Woelflingseder, Rolf Müller, Didac Carmona-Gutierrez, Tobias Madl, Sabrina Büttner, Kai-Uwe Fröhlich, Andrej Shevchenko, Tobias Eisenberg
Acetyl-CoA carboxylase 1-dependent lipogenesis promotes autophagy downstream of AMPK.
J Biol Chem, 294(32) 12020-12039 (2019)
PubMed Source   

Autophagy, a membrane-dependent catabolic process, ensures survival of aging cells and depends on the cellular energetic status. Acetyl-CoA carboxylase 1 (Acc1) connects central energy metabolism to lipid biosynthesis and is rate-limiting for the de novo synthesis of lipids. However, it is unclear how de novo lipogenesis and its metabolic consequences affect autophagic activity. Here, we show that in aging yeast, autophagy levels highly depend on the activity of Acc1. Constitutively active Acc1 (acc1S/A ) or a deletion of the Acc1 negative regulator, Snf1 (yeast AMPK), shows elevated autophagy levels, which can be reversed by the Acc1 inhibitor soraphen A. Vice versa, pharmacological inhibition of Acc1 drastically reduces cell survival and results in the accumulation of Atg8-positive structures at the vacuolar membrane, suggesting late defects in the autophagic cascade. As expected, acc1S/A cells exhibit a reduction in acetate/acetyl-CoA availability along with elevated cellular lipid content. However, concomitant administration of acetate fails to fully revert the increase in autophagy exerted by acc1S/A Instead, administration of oleate, while mimicking constitutively active Acc1 in WT cells, alleviates the vacuolar fusion defects induced by Acc1 inhibition. Our results argue for a largely lipid-dependent process of autophagy regulation downstream of Acc1. We present a versatile genetic model to investigate the complex relationship between acetate metabolism, lipid homeostasis, and autophagy and propose Acc1-dependent lipogenesis as a fundamental metabolic path downstream of Snf1 to maintain autophagy and survival during cellular aging.
@article{Gross7439,
author={Angelina S Gross, Andreas Zimmermann, Tobias Pendl, Sabrina Schroeder, Hannes Schoenlechner, Oskar Knittelfelder, Laura Lamplmayr, Ana Santiso, Andreas Aufschnaiter, Daniel Waltenstorfer, Sandra Ortonobes Lara, Sarah Stryeck, Christina Kast, Christoph Ruckenstuhl, Sebastian J Hofer, Birgit Michelitsch, Martina Woelflingseder, Rolf Müller, Didac Carmona-Gutierrez, Tobias Madl, Sabrina Büttner, Kai-Uwe Fröhlich, Andrej Shevchenko, Tobias Eisenberg},
title={Acetyl-CoA carboxylase 1-dependent lipogenesis promotes autophagy downstream of AMPK.},
journal ={The Journal of biological chemistry},
volume={294},
issue ={32},
pages={12020--12039},
year=2019
}

Seungmin Han, Juergen Fink, David J. Jörg, Eunmin Lee, Min Kyu Yum, Lemonia Chatzeli, Sebastian R Merker, Manon Josserand, Teodora Trendafilova, Amanda Andersson-Rolf, Catherine Dabrowska, Hyunki Kim, Ronald Naumann, Ji-Hyun Lee, Nobuo Sasaki, Richard Lester Mort, Onur Basak, Hans Clevers, Daniel E Stange, Anna Philpott, Jong Kyoung Kim, Benjamin D Simons, Bon-Kyoung Koo
Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells.
Cell Stem Cell, Art. No. doi: 10.1016/j.stem.2019.07.008 (2019)
PubMed Source   

The gastric corpus epithelium is the thickest part of the gastrointestinal tract and is rapidly turned over. Several markers have been proposed for gastric corpus stem cells in both isthmus and base regions. However, the identity of isthmus stem cells (IsthSCs) and the interaction between distinct stem cell populations is still under debate. Here, based on unbiased genetic labeling and biophysical modeling, we show that corpus glands are compartmentalized into two independent zones, with slow-cycling stem cells maintaining the base and actively cycling stem cells maintaining the pit-isthmus-neck region through a process of "punctuated" neutral drift dynamics. Independent lineage tracing based on Stmn1 and Ki67 expression confirmed that rapidly cycling IsthSCs maintain the pit-isthmus-neck region. Finally, single-cell RNA sequencing (RNA-seq) analysis is used to define the molecular identity and lineage relationship of a single, cycling, IsthSC population. These observations define the identity and functional behavior of IsthSCs.
@article{Han7480,
author={Seungmin Han, Juergen Fink, David J. Jörg, Eunmin Lee, Min Kyu Yum, Lemonia Chatzeli, Sebastian R Merker, Manon Josserand, Teodora Trendafilova, Amanda Andersson-Rolf, Catherine Dabrowska, Hyunki Kim, Ronald Naumann, Ji-Hyun Lee, Nobuo Sasaki, Richard Lester Mort, Onur Basak, Hans Clevers, Daniel E Stange, Anna Philpott, Jong Kyoung Kim, Benjamin D Simons, Bon-Kyoung Koo},
title={Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells.},
journal ={Cell stem cell},
volume={},
pages={null--null},
year=2019
}

Anna Bajur, K Venkatesan Iyer, Elisabeth Knust
Cytocortex-dependent dynamics of Drosophila Crumbs controls junctional stability and tension during germ band retraction.
J Cell Sci, 132(15) Art. No. doi: 10.1242/jcs.228338 (2019)
PubMed Source   

During morphogenesis, epithelia undergo dynamic rearrangements, which requires continuous remodelling of junctions and cell shape, but at the same time mechanisms preserving cell polarity and tissue integrity. Apico-basal polarity is key for the localisation of the machinery that enables cell shape changes. The evolutionarily conserved Drosophila Crumbs protein is critical for maintaining apico-basal polarity and epithelial integrity. How Crumbs is maintained in a dynamically developing embryo remains largely unknown. Here, we applied quantitative fluorescence techniques to show that, during germ band retraction, Crumbs dynamics correlates with the morphogenetic activity of the epithelium. Genetic and pharmacological perturbations revealed that the mobile pool of Crumbs is fine-tuned by the actomyosin cortex in a stage-dependent manner. Stabilisation of Crumbs at the plasma membrane depends on a proper link to the actomyosin cortex via an intact FERM-domain-binding site in its intracellular domain, loss of which leads to increased junctional tension and higher DE-cadherin (also known as Shotgun) turnover, resulting in impaired junctional rearrangements. These data define Crumbs as a mediator between polarity and junctional regulation to orchestrate epithelial remodelling in response to changes in actomyosin activity.This article has an associated First Person interview with the first author of the paper.
@article{Bajur7462,
author={Anna Bajur, K Venkatesan Iyer, Elisabeth Knust},
title={Cytocortex-dependent dynamics of Drosophila Crumbs controls junctional stability and tension during germ band retraction.},
journal ={Journal of cell science},
volume={132},
issue ={15},
pages={null--null},
year=2019
}

Kassiani Skouloudaki, Ioannis Christodoulou, Dilan Khalili, Vasilios Tsarouhas, Christos Samakovlis, Pavel Tomancak, Elisabeth Knust, Dimitrios Papadopoulos
Yorkie controls tube length and apical barrier integrity during airway development.
J Cell Biol, 218(8) 2762-2781 (2019)
PubMed Source   

Epithelial organ size and shape depend on cell shape changes, cell-matrix communication, and apical membrane growth. The Drosophila melanogaster embryonic tracheal network is an excellent model to study these processes. Here, we show that the transcriptional coactivator of the Hippo pathway, Yorkie (YAP/TAZ in vertebrates), plays distinct roles in the developing Drosophila airways. Yorkie exerts a cytoplasmic function by binding Drosophila Twinstar, the orthologue of the vertebrate actin-severing protein Cofilin, to regulate F-actin levels and apical cell membrane size, which are required for proper tracheal tube elongation. Second, Yorkie controls water tightness of tracheal tubes by transcriptional regulation of the δ-aminolevulinate synthase gene (Alas). We conclude that Yorkie has a dual role in tracheal development to ensure proper tracheal growth and functionality.
@article{Skouloudaki7442,
author={Kassiani Skouloudaki, Ioannis Christodoulou, Dilan Khalili, Vasilios Tsarouhas, Christos Samakovlis, Pavel Tomancak, Elisabeth Knust, Dimitrios Papadopoulos},
title={Yorkie controls tube length and apical barrier integrity during airway development.},
journal ={The Journal of cell biology},
volume={218},
issue ={8},
pages={2762--2781},
year=2019
}

Christian Franke, Urska Repnik, Sandra Segeletz, Nicolas Brouilly, Yannis Kalaidzidis, Jean-Marc Verbavatz, Marino Zerial
Correlative single-molecule localization microscopy and electron tomography reveals endosome nanoscale domains.
Traffic, 20(8) 601-617 (2019)
PubMed Source   

Many cellular organelles, including endosomes, show compartmentalization into distinct functional domains, which, however, cannot be resolved by diffraction-limited light microscopy. Single molecule localization microscopy (SMLM) offers nanoscale resolution but data interpretation is often inconclusive when the ultrastructural context is missing. Correlative light electron microscopy (CLEM) combining SMLM with electron microscopy (EM) enables correlation of functional subdomains of organelles in relation to their underlying ultrastructure at nanometer resolution. However, the specific demands for EM sample preparation and the requirements for fluorescent single-molecule photo-switching are opposed. Here, we developed a novel superCLEM workflow that combines triple-color SMLM (dSTORM & PALM) and electron tomography using semi-thin Tokuyasu thawed cryosections. We applied the superCLEM approach to directly visualize nanoscale compartmentalization of endosomes in HeLa cells. Internalized, fluorescently labeled Transferrin and EGF were resolved into morphologically distinct domains within the same endosome. We found that the small GTPase Rab5 is organized in nanodomains on the globular part of early endosomes. The simultaneous visualization of several proteins in functionally distinct endosomal sub-compartments demonstrates the potential of superCLEM to link the ultrastructure of organelles with their molecular organization at nanoscale resolution.
@article{Franke7440,
author={Christian Franke, Urska Repnik, Sandra Segeletz, Nicolas Brouilly, Yannis Kalaidzidis, Jean-Marc Verbavatz, Marino Zerial},
title={Correlative single-molecule localization microscopy and electron tomography reveals endosome nanoscale domains.},
journal ={Traffic (Copenhagen, Denmark)},
volume={20},
issue ={8},
pages={601--617},
year=2019
}

Pietro Incardona, Antonio Leo, Yaroslav Zaluzhnyi, Rajesh Ramaswamy, Ivo F. Sbalzarini
OpenFPM: A scalable open framework for particle and particle-mesh codes on parallel computers
Comput Phys Commun, 241 155-177 (2019)
  Source  

@article{Incardona7392,
author={Pietro Incardona, Antonio Leo, Yaroslav Zaluzhnyi, Rajesh Ramaswamy, Ivo F. Sbalzarini},
title={OpenFPM: A scalable open framework for particle and particle-mesh codes on parallel computers},
journal ={Computer Physics Communications},
volume={241},
pages={155--177},
year=2019
}

Laura Mediani, Jordina Guillén-Boixet, Jonathan Vinet, Titus Franzmann, Ilaria Bigi, Daniel Mateju, Arianna D Carrà, Federica F Morelli, Tatiana Tiago, Ina Poser, Simon Alberti, Serena Carra
Defective ribosomal products challenge nuclear function by impairing nuclear condensate dynamics and immobilizing ubiquitin.
EMBO J, 38(15) Art. No. e101341 (2019)
PubMed Source   

Nuclear protein aggregation has been linked to genome instability and disease. The main source of aggregation-prone proteins in cells is defective ribosomal products (DRiPs), which are generated by translating ribosomes in the cytoplasm. Here, we report that DRiPs rapidly diffuse into the nucleus and accumulate in nucleoli and PML bodies, two membraneless organelles formed by liquid-liquid phase separation. We show that nucleoli and PML bodies act as dynamic overflow compartments that recruit protein quality control factors and store DRiPs for later clearance. Whereas nucleoli serve as constitutive overflow compartments, PML bodies are stress-inducible overflow compartments for DRiPs. If DRiPs are not properly cleared by chaperones and proteasomes due to proteostasis impairment, nucleoli undergo amyloidogenesis and PML bodies solidify. Solid PML bodies immobilize 20S proteasomes and limit the recycling of free ubiquitin. Ubiquitin depletion, in turn, compromises the formation of DNA repair compartments at fragile chromosomal sites, ultimately threatening cell survival.
@article{Mediani7434,
author={Laura Mediani, Jordina Guillén-Boixet, Jonathan Vinet, Titus Franzmann, Ilaria Bigi, Daniel Mateju, Arianna D Carrà, Federica F Morelli, Tatiana Tiago, Ina Poser, Simon Alberti, Serena Carra},
title={Defective ribosomal products challenge nuclear function by impairing nuclear condensate dynamics and immobilizing ubiquitin.},
journal ={The EMBO journal},
volume={38},
issue ={15},
pages={null--null},
year=2019
}

Elisa Maria Rieckhoff, Keisuke Ishihara, Jan Brugués
How to tune spindle size relative to cell size?
Curr Opin Cell Biol, 60 139-144 (2019)
PubMed Source   

Cells need to regulate the size and shape of their organelles for proper function. For example, the mitotic spindle adapts its size to changes in cell size over several orders of magnitude, but we lack a mechanistic understanding of how this is achieved. Here, we review our current knowledge of how small and large spindles assemble and ask which microtubule-based biophysical processes (nucleation, polymerization dynamics, transport) may be responsible for spindle size regulation. Finally, we review possible cell-scale mechanisms that put spindle size under the regulation of cell size.
@article{Rieckhoff7467,
author={Elisa Maria Rieckhoff, Keisuke Ishihara, Jan Brugués},
title={How to tune spindle size relative to cell size?},
journal ={Current opinion in cell biology},
volume={60},
pages={139--144},
year=2019
}

Madeline Lancaster, Meritxell Huch
Disease modelling in human organoids.
Dis Model Mech, 12(7) Art. No. dmm039347 (2019)
PubMed Source   

The past decade has seen an explosion in the field of in vitro disease modelling, in particular the development of organoids. These self-organizing tissues derived from stem cells provide a unique system to examine mechanisms ranging from organ development to homeostasis and disease. Because organoids develop according to intrinsic developmental programmes, the resultant tissue morphology recapitulates organ architecture with remarkable fidelity. Furthermore, the fact that these tissues can be derived from human progenitors allows for the study of uniquely human processes and disorders. This article and accompanying poster highlight the currently available methods, particularly those aimed at modelling human biology, and provide an overview of their capabilities and limitations. We also speculate on possible future technological advances that have the potential for great strides in both disease modelling and future regenerative strategies.
@article{Lancaster7478,
author={Madeline Lancaster, Meritxell Huch},
title={Disease modelling in human organoids.},
journal ={Disease models & mechanisms},
volume={12},
issue ={7},
pages={null--null},
year=2019
}

Adrian Pascal Nievergelt, Gonzalo Alvarez Viar, Gaia Pigino
Towards a mechanistic understanding of cellular processes by cryoEM.
Curr. Opin. Struct. Biol., 58 149-158 (2019)
PubMed Source   

A series of recent hardware and software developments have transformed cryo-electron microscopy (cryoEM) from a niche tool into a method that has become indispensable in structural and functional biology. Samples that are rapidly frozen are encased in a near-native state inside a layer of amorphous ice, and then imaged in an electron microscope cooled to cryogenic temperatures. Despite being conceptually simple, cryoEM owns its success to a plethora of technological developments from numerous research groups. Here, we review the key technologies that have made this astonishing transformation possible and highlight recent trends with a focus on cryo-electron tomography. Additionally, we discuss how correlated microscopy is an exciting and perpendicular development route forward in this already rapidly growing field. We specifically discuss microscopy techniques that allow to complement time-dependent information of dynamic processes to the unique high resolution obtained in cryoEM.
@article{Nievergelt7466,
author={Adrian Pascal Nievergelt, Gonzalo Alvarez Viar, Gaia Pigino},
title={Towards a mechanistic understanding of cellular processes by cryoEM.},
journal ={Current opinion in structural biology},
volume={58},
pages={149--158},
year=2019
}