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Chemical Biology

  • <em>C9ORF72</em>-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neurons
    Open Access
    C9ORF72-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neurons

    Paolo M Marchi, Lara Marrone, Laurent Brasseur, Audrey Coens, Christopher P Webster, Luc Bousset, Marco Destro, Emma F Smith, Christa G Walther, Victor Alfred, Raffaele Marroccella, Emily J Graves, Darren Robinson, Allan C Shaw, Lai Mei Wan, Andrew J Grierson, Stephen J Ebbens, Kurt J De Vos, Guillaume M Hautbergue, Laura Ferraiuolo, Ronald Melki, Mimoun Azzouz

    Paolo M Marchi ... Mimoun Azzouz

    Published 13 May 2022

    Extracellularly delivered poly-GAs are internalised into astrocytes via an endocytosis-dependent pathway and then spread to motor neurons, implying non-cell autonomous mechanisms in C9ORF72-ALS/FTD.

  • Adipose tissue–specific ablation of Ces1d causes metabolic dysregulation in mice
    Open Access
    Adipose tissue–specific ablation of Ces1d causes metabolic dysregulation in mice

    Gang Li, Xin Li, Li Yang, Shuyue Wang, Yulin Dai, Baharan Fekry, Lucas Veillon, Lin Tan, Rebecca Berdeaux, Kristin Eckel-Mahan, Philip L Lorenzi, Zhongming Zhao, Richard Lehner, Kai Sun

    Gang Li ... Kai Sun

    Published 22 April 2022

    Ces1d is a crucial enzyme in adipose tissue. Here, we found a high level of Ces1d translocates onto lipid droplets where it digests the lipids to produce unique fatty acids which are key for glucose and lipid metabolism.

  • Nucleotide biosynthesis links glutathione metabolism to ferroptosis sensitivity
    Open Access
    Nucleotide biosynthesis links glutathione metabolism to ferroptosis sensitivity

    Amy Tarangelo, Jason Rodencal, Joon Tae Kim, Leslie Magtanong, Jonathan Z Long, Scott J Dixon

    Amy Tarangelo ... Scott J Dixon

    Published 24 January 2022

    The tumor suppressor protein p53 inhibits ferroptosis by reducing the consumption of glutathione in nucleotide biosynthesis.

  • USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylation
    Open Access
    USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylation

    Emma V Rusilowicz-Jones, Jane Jardine, Andreas Kallinos, Adan Pinto-Fernandez, Franziska Guenther, Mariacarmela Giurrandino, Francesco G Barone, Katy McCarron, Christopher J Burke, Alejandro Murad, Aitor Martinez, Elena Marcassa, Malte Gersch, Alexandre J Buckmelter, Katherine J Kayser-Bricker, Frederic Lamoliatte, Akshada Gajbhiye, Simon Davis, Hannah C Scott, Emma Murphy, Katherine England, Heather Mortiboys, David Komander, Matthias Trost, Benedikt M Kessler, Stephanos Ioannidis, Michael K Ahlijanian, Sylvie Urbé, Michael J Clague

    Emma V Rusilowicz-Jones ... Michael J Clague

    Published 7 July 2020

    A new inhibitor of the deubiquitylase USP30, an actionable target relevant to Parkinson’s Disease, is introduced and characterised for parameters related to mitophagy.

  • Caspase-1 interdomain linker cleavage is required for pyroptosis
    Open Access
    Caspase-1 interdomain linker cleavage is required for pyroptosis

    Daniel P Ball, Cornelius Y Taabazuing, Andrew R Griswold, Elizabeth L Orth, Sahana D Rao, Ilana B Kotliar, Lauren E Vostal, Darren C Johnson, Daniel A Bachovchin

    Daniel P Ball ... Daniel A Bachovchin

    Published 12 February 2020

    The related human NLRP1 and CARD8 form ASC-dependent and ASC-independent inflammasomes, respectively, both of which require pro-caspase-1 interdomain linker processing for the induction of pyroptosis.

  • Phenotypic proteomic profiling identifies a landscape of targets for circadian clock–modulating compounds
    Open Access
    Phenotypic proteomic profiling identifies a landscape of targets for circadian clock–modulating compounds

    Sandipan Ray, Radoslaw Lach, Kate J Heesom, Utham K Valekunja, Vesela Encheva, Ambrosius P Snijders, Akhilesh B Reddy

    Sandipan Ray ... Akhilesh B Reddy

    Published 2 December 2019

    This study provides comprehensive insights into the mechanism of action and cellular effects of circadian period–modulating compounds, which is critical for clearly defining molecular targets to modulate daily rhythms for therapeutic benefit.

  • Plasmalogen loss caused by remodeling deficiency in mitochondria
    Open Access
    Plasmalogen loss caused by remodeling deficiency in mitochondria

    Tomohiro Kimura, Atsuko K Kimura, Mindong Ren, Vernon Monteiro, Yang Xu, Bob Berno, Michael Schlame, Richard M Epand

    Tomohiro Kimura ... Richard M Epand

    Published 21 August 2019

    31P NMR unveils cell type–dependent losses of plasmalogen in the chain remodeling–deficient brain, liver, kidney, and lymphoblast in association with aberrant mitochondrial function and morphology.

  • Ncl1-mediated metabolic rewiring critical during metabolic stress
    Open Access
    Ncl1-mediated metabolic rewiring critical during metabolic stress

    Ajay Bhat, Rahul Chakraborty, Khushboo Adlakha, Ganesh Agam, Kausik Chakraborty, Shantanu Sengupta

    Ajay Bhat ... Shantanu Sengupta

    Published 15 August 2019

    Accumulation of cysteine induces translational defects and metabolic rewiring that are abrogated by leucine in a transfer RNA (tRNA) methyltransferase NCL1-dependent manner in yeast.

  • Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunit
    Open Access
    Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunit

    Prashant Khandagale, Doureradjou Peroumal, Kodavati Manohar, Narottam Acharya

    Prashant Khandagale ... Narottam Acharya

    Published 18 March 2019

    The subunit p12 of human DNA polymerase delta (hPolδ) can dimerize, facilitating its interaction with PCNA and suggesting that hPolδ exists in a pentameric form in the cell.

  • Chemical genetic identification of GAK substrates reveals its role in regulating Na<sup>+</sup>/K<sup>+</sup>-ATPase
    Open Access
    Chemical genetic identification of GAK substrates reveals its role in regulating Na+/K+-ATPase

    Amy W Lin, Kalbinder K Gill, Marisol Sampedro Castañeda, Irene Matucci, Noreen Eder, Suzanne Claxton, Helen Flynn, Ambrosius P Snijders, Roger George, Sila K Ultanir

    Amy W Lin ... Sila K Ultanir

    Published 31 December 2018

    Novel GAK phosphorylation targets are identified using chemical genetic methods. One of the substrates is the α subunit of the Na+/K+-ATPase, phosphorylation of which is necessary for its surface trafficking from endosomes. Conserved functions of NAK family kinases are described.

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  • Systems & Computational Biology (64)
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