Stress signalling articles within Nature Communications

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  • Article
    | Open Access

    H2O2 stress is known to activate a slew of transcription factors that restore redox balance. Here, the authors use live-cell imaging and single-cell analysis to reveal that the transcription factors that are activated and their timing of activation is dose dependent.

    • Elizabeth Jose
    • , Woody March-Steinman
    •  & Andrew L. Paek

  • Article
    | Open Access

    The African trypanosome Trypanosoma brucei has been shown to form stress granules in vitro that might be repurposed to enable differentiation and facilitate parasite transmission. Here, Cayla et al. show that differentiation between slender and stumpy forms does involve membrane-less granules that are different from nutritional stress granules.

    • Mathieu Cayla
    • , Christos Spanos
    •  & Keith R. Matthews

  • Article
    | Open Access

    How tissues adapt to extreme cold is not well understood. Here, the authors discover a mechanism that promotes FOXO1-mediated cold survival gene transcription at low temperatures, with potential implications for long-term tissue storage for transplantation.

    • Xiaomei Zhang
    • , Lihao Ge
    •  & Jingxing Ou

  • Article
    | Open Access

    Nuclear DNA damage downstream of mitochondrial ROS is often cited to contribute to cancer initiation and aging. However, here the authors show that although H2O2 induces DNA mutations when produced near DNA, it does not when released by mitochondria.

    • Daan M. K. van Soest
    • , Paulien E. Polderman
    •  & Tobias B. Dansen

  • Comment
    | Open Access

    Contact between organelles such as the mitochondria (Mito) and endoplasmic reticulum (ER) is crucial to coordinate vital cellular homeostatic processes. Here we discuss recent work showing that Mito-ER proximity is regulated by heterotypic complexes between the F-actin polymerizing protein Diaphanous-1) and the mitochondrial dynamics protein Mitofusin 2, which confers increased susceptibility to ischemia/reperfusion injury.

    • Lorrie A. Kirshenbaum
    • , Rimpy Dhingra
    •  & Sergio Lavandero

  • Article
    | Open Access

    The RAD51 recombinase plays a pivotal role in replication fork reversal during replication stress. Here, the authors show that the GCFC domain-containing protein TFIP11 interacts with BLM helicase and is important for fork reversal during replication stress to preserve genome stability.

    • Junliang Chen
    • , Mingjie Wu
    •  & Ting Liu

  • Article
    | Open Access

    Mitochondrial biogenesis and maintenance relies on protein import from the cytosol. Here, authors show that import failure impacts organelle structure and dynamics. They also identify a rescue mechanism involving intercellular mitochondrial transfer.

    • Hope I. Needs
    • , Emily Glover
    •  & Ian Collinson

  • Article
    | Open Access

    Genetic code expansion (GCE) is a protein engineering tool that enables programmed and site-specific installation of noncanonical amino acids into proteins. Here, authors show that cellular stress remodelling boosts GCE in mammalian cells including GCE realized by orthogonally translating organelles.

    • Mikhail E. Sushkin
    • , Christine Koehler
    •  & Edward A. Lemke

  • Article
    | Open Access

    Targeting ribosome biogenesis with the ribosome inhibitor, homoharringtonine (HHT), is effective in leukaemia but not in solid tumours. Here, the authors demonstrate that in solid tumours, activation of JNK signaling following HHT-induced ribosomal stress promotes Snail1 accumulation in the nucleolus which facilitates ribosome biogenesis and resistance to HHT.

    • Kewei Qin
    • , Shuhan Yu
    •  & Yong Yi

  • Article
    | Open Access

    The integrated stress response (ISR) is the focus of numerous investigations and drug development programs. Here, the authors show that ATP-competitive inhibitors of ISR kinases PERK, PKR and GCN2 inhibit their targets but activate the ISR by directly binding to and activating a sister ISR kinase.

    • Maria Szaruga
    • , Dino A. Janssen
    •  & Anne Bertolotti

  • Article
    | Open Access

    Chemotherapy can cause severe damage to cardiomyocytes in some patients but it is unclear how cardiomyocytes protect themselves against such stress. Here the authors show that cardiomyocytes initiate an endogenous protective response when exposed to chemotherapeutic agents by translocating mitochondrial enzymes to the nucleus.

    • Shubhi Srivastava
    • , Priyanka Gajwani
    •  & Jalees Rehman

  • Article
    | Open Access

    Mitochondrial function has been linked to immunity but the role of the Krebs’s cycle in regards the immune response is not well characterised. Here the authors show that Krebs’s cycle enzyme ACO2 suppresses immunity via modulation of oxaloacetate and the mitochondrial unfolded protein response.

    • Eunah Kim
    • , Andrea Annibal
    •  & Seung-Jae V. Lee

  • Article
    | Open Access

    Cellular redox homeostasis is important when responding to environmental changes. Here, the authors demonstrate APT1 is a redox sensor in plant defense and identify a pathway for oxidative stress resistance.

    • Tuo Ji
    • , Lihua Zheng
    •  & Tao Wang

  • Article
    | Open Access

    Exposure to irreparable stresses induces transient ciliogenesis, enabling communication with PML-NBs via a FBF1 pathway to trigger senescence in mammalian cells. Fbf1 ablation reduces senescence and associated health decline in mice, highlighting cilia as a promising senotherapy target.

    • Xiaoyu Ma
    • , Yingyi Zhang
    •  & Jinghua Hu

  • Article
    | Open Access

    DNA damage-induced micronuclei are linked to downstream viral signalling through the cGAS pattern recognition receptor. Here, the authors identify features of micronuclei chromatin that determine cGAS-MN recruitment and associated pathway activation.

    • Kate M. MacDonald
    • , Shirony Nicholson-Puthenveedu
    •  & Shane M. Harding

  • Article
    | Open Access

    The recently described protein HAPSTR1 governs cellular stress resilience. Here, the authors discover a mammalian HAPSTR1 paralog, called HAPSTR2, which formed via retro-transposition and operates to augment and buffer cellular stress signaling.

    • David R. Amici
    • , Harun Cingoz
    •  & Marc L. Mendillo

  • Article
    | Open Access

    The molecular mechanisms underlying response to chemotherapy in Acute myeloid leukemia (AML) remain to be explored. Here, the authors perform 36-dimensional mass cytometry in 32 AML patients during intensive chemotherapy and suggest functional signalling analysis for prognosis prediction early after treatment in AML.

    • Benedicte Sjo Tislevoll
    • , Monica Hellesøy
    •  & Bjørn Tore Gjertsen

  • Article
    | Open Access

    Plasma cells are terminally differentiated B cells that are specialized for antibody secretion. Authors show here that genomic deletion of the p38α mitogen activated protein kinase specifically in the B cell lineage leads to diminished plasma cell differentiation via impairment of a transcriptional regulatory program by BLIMP1.

    • Jianfeng Wu
    • , Kang Yang
    •  & Jiahuai Han

  • Article
    | Open Access

    Pancreatic β-cells are naturally prone to ER stress due to their role in insulin production and secretion. Here, the authors show that chronic ER stress adaptive exhaustion results in an irreversible loss of β-cell function leading to T1D pathogenesis

    • Chien-Wen Chen
    • , Bo-Jhih Guan
    •  & Maria Hatzoglou

  • Article
    | Open Access

    Here the authors revealed a role for the protein deacetylase SIRT2 in Golgi stress, particularly induced by bacterial infection. Shigella secrete effector proteins such as IcsB, which transfers fatty acyl groups to modify host proteins to evade host immune surveillance. The upregulated SIRT2 counteracts this function by removing the fatty acyl groups and enhancing the killing of Shigella.

    • Miao Wang
    • , Yugang Zhang
    •  & Hening Lin

  • Article
    | Open Access

    Multiplex analyses of samples allow understanding complex processes in cancer initiation, progression and therapy response. Here, the authors present a fluorescence imaging-based visual barcode for livecell clonal-multiplexing which allows identifying signalling pathways clusters in response to different chemotherapy compounds.

    • Tom Kaufman
    • , Erez Nitzan
    •  & Ravid Straussman

  • Article
    | Open Access

    Human mitochondria experience substantial stress and malfunction in neurological diseases. Here, the authors reveal DELE1 as a multimodal sensor of protein import and processing defects, rationalizing mitochondrial stress integration.

    • Evelyn Fessler
    • , Luisa Krumwiede
    •  & Lucas T. Jae

  • Article
    | Open Access

    In Drosophila, ER-targeted mRNAs are degraded by Ire1-dependent pathway. Here the authors report that the fly mRNA binding protein Pumilio is phosphorylated by Ire1 and binds to Xbp1 mRNA, protecting it from the non-canonical endoribonuclease activity of Ire1.

    • Fátima Cairrão
    • , Cristiana C. Santos
    •  & Pedro M. Domingos

  • Article
    | Open Access

    Hypoxia induces mitochondrial clearance and autophagy, although the upstream mechanisms are not well defined. Here, the authors identify that oxygen-sensitive methylation of the key autophagy regulator ULK1 promotes ULK1 activation and subsequent autophagosome formation and mitochondrial clearance.

    • Jingyi Li
    • , Tao Zhang
    •  & Rui Liu

  • Article
    | Open Access

    High-calorie diet promotes thiol oxidative stress and the reprogramming of blood monocytes, giving rise to obesogenic and proatherogenic macrophages. Here the authors report that loss of monocytic thiol transferase glutaredoxin 1 results in the derepression of sex-specific oxidative stress responses in macrophages, promoting atherogenesis and obesity in female mice.

    • Yong Joo Ahn
    • , Luxi Wang
    •  & Reto Asmis

  • Article
    | Open Access

    Signalling through the IRE1 arm of the unfolded protein response exerts both protective and harmful effects in obesity. Here the authors report that a selective pharmacologic activator of IRE1/XBP1s signalling stimulates an adaptive remodelling of liver and pancreas in diet-induced obese mice and mitigates obesity-linked systemic metabolic dysfunction.

    • Aparajita Madhavan
    • , Bernard P. Kok
    •  & R. Luke Wiseman

  • Article
    | Open Access

    Ionizing radiation and chemotherapy deplete haematopoietic stem cells and damage the vascular niche. Here the authors show that irradiation induces SEMA3A secretion from bone marrow endothelial cells (ECs), inducing EC apoptosis via NRP1 and that NRP1 inhibition promotes vascular regeneration and R spondin 2 dependent hematopoietic regeneration.

    • Christina M. Termini
    • , Amara Pang
    •  & John P. Chute

  • Article
    | Open Access

    PKCε is known to exert a role in genome protection by directly phosphorylating and switching the specificity of Aurora B. Here the authors identify SERBP1 as a parallel mitotic PKCε substrate controlling translation and ensuring the integrity of chromosome segregation and successful cell division.

    • Silvia Martini
    • , Khalil Davis
    •  & Peter J. Parker

  • Article
    | Open Access

    A major question in redox signaling is how H2O2 oxidizes target protein thiols in the presence of glutathione peroxidases and peroxiredoxins. We reveal signaling by H2O2 via its enzymatic conversion to an alkyl hydroperoxide that stereo-specifically escapes peroxidases and oxidizes target proteins.

    • Raphael F. Queiroz
    • , Christopher P. Stanley
    •  & Roland Stocker

  • Article
    | Open Access

    The immune response to herpes simplex virus is essential in limiting immunopathology during infection, however factors linked to neuroprotection are currently unclear. Here the authors implicate mTORC2 in the host response to viral infection and link to neuroprotection.

    • Rahul K. Suryawanshi
    • , Chandrashekhar D. Patil
    •  & Deepak Shukla

  • Article
    | Open Access

    Most mutant p53 heterozygous tumours undergo loss of the remaining wildtype (WT) p53 allele which leads to stabilization of the mutant p53 protein. Here, the authors show in an autochthonous colorectal cancer model that the WT p53 allele retains partial activity and suppresses the heat shock factor 1 (HSF1)- chaperone axis to prevent mutant p53 stabilisation and mutant p53 gain-of-function activities, thereby creating selective pressure for p53 loss-of-heterozygosity.

    • Tamara Isermann
    • , Özge Çiçek Şener
    •  & Ramona Schulz-Heddergott

  • Article
    | Open Access

    How dynamic transcription factors temporally interact to regulate stress survival in yeast is currently unclear. Here the authors integrate single-cell imaging, RNA-seq, and modeling to identify a new cell fate control mechanism mediated by temporal redundancy modulation during yeast stress response.

    • Yan Wu
    • , Jiaqi Wu
    •  & Yihan Lin

  • Article
    | Open Access

    Mitochondria play a pivotal role in the generation of signals coupling metabolism with neurotransmitter release, though underlying mechanisms remain unknown. Here the authors show that endogenously produced hydrogen peroxide originating from axonal mitochondria functions as a signaling cue to selectively regulate neuropeptide secretion in C. elegans.

    • Qi Jia
    •  & Derek Sieburth

  • Article
    | Open Access

    Histone acetylations are important epigenetic marks for transcriptional activation and respond to metabolic changes. Here the authors develop a lifespan screen and show that inactivation of the histone deacetylase complex activates longevity and protects against stress via trehalose metabolism.

    • Ruofan Yu
    • , Xiaohua Cao
    •  & Weiwei Dang

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