Cell death articles within Nature Communications

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  • Article
    | Open Access

    Kidney stone disease is caused by accumulation of oxalate crystals, which trigger tissue injury, inflammation and cell death. Mulay et al. show that crystals induce cell death in the kidney through necroptosis, and propose that this pathway may be a target for the treatment of crystal-induced disease.

    • Shrikant R. Mulay
    • , Jyaysi Desai
    •  & Hans-Joachim Anders

  • Article
    | Open Access

    The TCOF1 gene is mutated in Treacher Collin's syndrome, a congenital craniofacial syndrome. Here, the authors show that Tcof1loss-of-function results in oxidative stress induced DNA damage and neuroepithelial cell death, and addition of antioxidants to pregnant mutant mice protected against these defects.

    • Daisuke Sakai
    • , Jill Dixon
    •  & Paul A. Trainor

  • Article
    | Open Access

    Proteinuria promotes chronic kidney disease progression. Karoui et al. show that proteinuria stimulates overexpression of iron transporting protein lipocalin-2 via Ca2+release-induced ER stress, which leads to tubular apoptosis, and that inhibition of this pathway by PBA delays renal deterioration in proteinuric mice.

    • Khalil El Karoui
    • , Amandine Viau
    •  & Fabiola Terzi

  • Article
    | Open Access

    Cytoplasmic stress granules (SG) are intracellular aggregates that suppress translation and sequester apoptosis regulatory factors. Here the authors show that reactive oxygen species oxidise the SG-nucleating protein TIA1, preventing SG formation and promoting apoptosis in the presence of additional stress.

    • Kyoko Arimoto-Matsuzaki
    • , Haruo Saito
    •  & Mutsuhiro Takekawa

  • Article
    | Open Access

    Several histone modifiers have been implicated in the survival of multiple myeloma cells. Here, the authors reveal a role for the histone demethylase KDM3A in the survival of this haematologic cancer, and show that mechanistically KDM3A removes H3K9 methylation from the promoters of KLF2 and IRF4, genes essential for myeloma cell survival.

    • Hiroto Ohguchi
    • , Teru Hideshima
    •  & Kenneth C. Anderson

  • Article |

    Slow-dividing ‘loser’ cells are outcompeted by more robust ‘winner’ cells and eliminated by macrophage-like haemocytes in the fruit fly larva. Here the authors show that the dying loser cells secrete the enzyme Tyrosyl-tRNA synthetase that upon Mmp2-mediated cleavage acts as a haemocyte chemoattractant.

    • Sergio Casas-Tintó
    • , Fidel-Nicolás Lolo
    •  & Eduardo Moreno

  • Article
    | Open Access

    Programed cell death occurs in a stereotypic fashion duringC. elegansdevelopment, and it is thought that engulfment promotes programmed cell death. Here the authors present evidence that a signaling function of the conserved engulfment pathways, not the process of engulfment itself, promotes apoptotic cell death.

    • Sayantan Chakraborty
    • , Eric J. Lambie
    •  & Barbara Conradt

  • Article
    | Open Access

    The proapoptotic protein Bax triggers cell death by forming pores in the outer mitochondrial membrane. Using single-particle TIRF imaging, the authors show that Bax binds the membrane in a monomeric state before forming dimers and multimers of dimers, which are disassembled by the survival protein Bcl-xL.

    • Yamunadevi Subburaj
    • , Katia Cosentino
    •  & Ana J. García-Sáez

  • Article
    | Open Access

    Tumour cells can survive by evading cell death pathways and altering their metabolism to adapt to their local environment. In this study, Iansanteet al. show that the anti-apoptotic protein PARP14 maintains low PKM2 activity, leading to enhanced glycolysis, demonstrating a link between suppression of apoptosis and altered metabolism.

    • Valeria Iansante
    • , Pui Man Choy
    •  & Salvatore Papa

  • Article
    | Open Access

    Newts can regenerate amputated limbs via unknown mechanism involving dedifferentiation of cells in the stump into progenitors that contribute to the new appendages. Here the authors show that skeletal muscle dedifferentiation in regenerating newt limbs relies on a diverted programmed cell death response by myofibers.

    • Heng Wang
    • , Sara Lööf
    •  & András Simon

  • Article
    | Open Access

    ER stress is associated with the pathogenesis of chronic kidney disease (CKD) and new CKD therapies are needed. Here the authors show that expression of Rtn1 can control severity of renal disease and that inhibition of its expression can attenuate ER stress and CKD.

    • Ying Fan
    • , Wenzhen Xiao
    •  & John C. He

  • Article
    | Open Access

    Autophagy is a catabolic process whereby cellular components are degraded by the autophagosome, but the role of the actin cytoskeleton is not clear. Here Coutts and La Thangue show that the actin nucleator JMY is recruited to the autophagosome via binding LC3, and promotes actin nucleation that is required for autophagosome maturation.

    • Amanda S. Coutts
    •  & Nicholas B. La Thangue

  • Article
    | Open Access

    Reprogramming holds great promise for regenerative medicine but the molecular mechanisms governing the generation of induced pluripotent stem cells remain unclear. Here, the authors reveal functions for the axonal guidance cue Netrin-1 in constraining apoptosis at the early stage of reprogramming and in established pluripotent cells.

    • Duygu Ozmadenci
    • , Olivier Féraud
    •  & Fabrice Lavial

  • Article
    | Open Access

    CENP-E regulates chromosome alignment during mitosis to distribute chromosomes equally into daughter cells. Here, the authors show that CENP-E inhibition causes p53-mediated post-mitotic apoptosis in tumours where the spindle assembly checkpoint is compromised, suggesting that CENP-E is a therapeutic target for these cancers.

    • Akihiro Ohashi
    • , Momoko Ohori
    •  & Kentaro Iwata

  • Article |

    Unlike rodents, humans produce the protein Cidea in white adipose tissue, where it associates with lipid droplets. Here the authors generate mice that express human Cidea in fat tissues to show Cidea exerts beneficial metabolic effects by regulating the expansion of visceral fat in response to a high-fat diet.

    • Gustavo Abreu-Vieira
    • , Alexander W. Fischer
    •  & Natasa Petrovic

  • Article
    | Open Access

    KDEL receptors are known to be involved in retrotransporting chaperones to the endoplasmic reticulum from the Golgi complex. Here the authors unravel a role of KDEL receptor 1 in regulating integrated stress responses in naïve T cells through its association with protein phosphatase 1.

    • Daisuke Kamimura
    • , Kokichi Katsunuma
    •  & Masaaki Murakami

  • Article |

    Ovarian cancer is often accompanied by metastases at the time of diagnosis and has a poor survival rate. In this study, Aslan et al.identify a role for ZNF304 in ovarian cancer metastasis and show that the protein transcriptionally regulates β1 integrin, resulting in a reduction in programmed cell death.

    • Burcu Aslan
    • , Paloma Monroig
    •  & Gabriel Lopez-Berestein

  • Article
    | Open Access

    The tumour suppressor p53 is known to be inhibited by histone deacetylase 3 but the molecular mechanism is poorly understood. Here Choi et al. show regulation by programmed cell death 5 and an essential role in activating p53 following DNA damage.

    • Hyo-Kyoung Choi
    • , Youngsok Choi
    •  & Ho-Geun Yoon

  • Article
    | Open Access

    During apoptosis, cells break up into smaller fragments to facilitate removal. Here the authors characterize a beads-on-a-string structure formed by monocytes undergoing apoptosis in vitro, which shears into apoptotic bodies lacking nuclear contents, and is blocked by the antidepressant sertraline.

    • Georgia K. Atkin-Smith
    • , Rochelle Tixeira
    •  & Ivan K.H. Poon

  • Article |

    The microRNA miR-21 is overexpressed in cancer and is thought to function through anti-apoptotic activity. Here, Ma et al. show that deleting or blocking miR-21 in mice protects against acute pancreatitis and TNF-α-induced tissue damage by inhibiting RIP3-dependent regulated necrosis (necroptosis).

    • Xiaodong Ma
    • , Daniel J. Conklin
    •  & Yong Li

  • Article |

    Some normal and cancer stem cells are resistant to killing by genotoxins, but the mechanism for this resistance is poorly understood. Here the authors show that adult stem cells inDrosophila melanogastergermline and midgut are resistant to genotoxic stimuli and find that this is mediated by signalling via the receptor tyrosine kinase Tie released from apoptotic cells.

    • Yalan Xing
    • , Tin Tin Su
    •  & Hannele Ruohola-Baker

  • Article
    | Open Access

    Cellular functions of the vault complex, a large ribonucleoprotein assembly remain elusive. Here, the authors show that Epstein–Barr virus infection enhances the expression of the vault complex-associated RNAs, which leads to improved survival of infected cells due to the inhibition of cell apoptosis.

    • Melanie Amort
    • , Birgit Nachbauer
    •  & Norbert Polacek

  • Article
    | Open Access

    Cells experiencing extended mitotic arrest often undergo cell death as a result of steadily declining levels of the apoptotic inhibitor MCL1, but the mechanism controlling this process is poorly understood. Here, Haschka et al.show that the BH3-only protein NOXA promotes the degradation of MCL1, enabling BIM-dependent cell death.

    • Manuel D. Haschka
    • , Claudia Soratroi
    •  & Luca L. Fava

  • Article |

    During apoptosis, Bak undergoes major conformational changes that lead to mitochondrial permeabilization. Here, the authors characterize changes that occur within the Bak N-terminus using a series of antibodies and a novel tethering approach, demonstrating that dissociation of the α1 helix is a key early step in the unfolding of Bak.

    • Amber E. Alsop
    • , Stephanie C. Fennell
    •  & Ruth M. Kluck

  • Article |

    ATG7 promotes cardiomyocyte autophagy but the molecular mechanism of its regulation is unknown. Here, Wang et al.identify a long non-coding RNA dubbed autophagy promoting factor (APF) that binds and inhibits miR-188-3p, which in turn acts on ATG7, to regulate cardiac autophagy.

    • Kun Wang
    • , Cui-Yun Liu
    •  & Pei-Feng Li

  • Article
    | Open Access

    Several pathogenic fungi such as Candida albicans undergo transitions between single-celled forms and multicellular filaments. Here the authors perform a genome-scale analysis of C. albicansand show that, contrary to common belief, filamentation is not required for escape from host immune cells.

    • Teresa R. O’Meara
    • , Amanda O. Veri
    •  & Leah E. Cowen

  • Article |

    Nonsense-mediated mRNA decay (NMD) is a pathway that controls endogenous transcript levels and limits the production of aberrant mRNAs. Here the authors show that NMD is attenuated in cells treated with chemotherapeutic compounds through caspase-mediated proteolytic cleavage of UPF1, a key NMD effector.

    • Maximilian W. Popp
    •  & Lynne E. Maquat

  • Article
    | Open Access

    RIPK3 can cause necroptotic cell death via MLKL phosphorylation, and activate NLRP3 inflammasome. Here the authors show that MLKL is dispensable for NLRP3 activation by RIPK3, and highlight how different IAP proteins limit RIPK3 induced apoptosis, necroptosis and IL-1 secretion.

    • Kate E. Lawlor
    • , Nufail Khan
    •  & James E. Vince

  • Article |

    TAR DNA-binding protein of 43 kDa (TDP-43) and its C-terminal fragment of 25 kDa (CTF25) play critical roles in several neurodegenerative diseases but the cleavage site that generates CTF25 remains undetermined. Here the authors show that caspase-4 cleaves TDP-43 after Aps174 generating CTF25, and this leads to TDP-43 clearance and increased cell viability.

    • Quan Li
    • , Moe Yokoshi
    •  & Yukio Kawahara

  • Article
    | Open Access

    The earliest steps in autophagy are thought to include the budding of Atg16L-containing vesicles from the plasma membrane and their homotypic fusion to form a phagophore. Morozova et al. reveal a role for the membrane curvature-inducing protein Annexin A2 in the formation and fusion of these vesicles.

    • Kateryna Morozova
    • , Sunandini Sidhar
    •  & Laura Santambrogio

  • Article
    | Open Access

    The contribution of signal strength on cell fate decisions is often not reflected in signalling networks. By combining mathematical simulation and biochemical experiments in cultured adult cardiomyocytes, Shin et al. show that the concentration of a β-adrenergic receptor agonist affects the expression of Bcl-2, influencing the balance between cell survival and death.

    • Sung-Young Shin
    • , Taeyong Kim
    •  & Do Han Kim

  • Article |

    The poly(ADP-ribose) polymerase PARP13 targets RNA viruses by binding to viral RNA and promoting its degradation by cellular decay factors such as the exosome. Todorova et al. find that PARP13 also plays a much broader role as a regulator of host mRNA stability, and promotes apoptosis by degrading TRAILR4transcripts.

    • Tanya Todorova
    • , Florian J. Bock
    •  & Paul Chang

  • Article |

    The death receptor CD95/Fas induces apoptosis of many normal cells but prevents necrotic death of cancer cells. Here the authors demonstrate that CD95 activation promotes a cancer stem cell (CSC) phenotype, and that CSCs but not differentiated cancer cells are resistant to CD95-mediated apoptosis and depend on CD95 signalling to prevent necrosis.

    • Paolo Ceppi
    • , Abbas Hadji
    •  & Marcus E. Peter

  • Article
    | Open Access

    The process of controlled chromatin release from the nuclei of inflammatory cells to entrap and kill bacteria, termed ETosis, is important in innate immunity in vertebrates. Here the authors demonstrate that ETosis, mediated by hematocytes, also contributes to defence mechanisms in invertebrates.

    • Calum T. Robb
    • , Elisabeth A. Dyrynda
    •  & Valerie J. Smith

  • Article |

    The transcription factor Wilms’ tumour 1 (WT1) regulates kidney development, and Wt1 mutations are associated with renal cancer. Here the authors identify WT1 target genes in renal progenitors during early kidney development in mouse embryos and show that loss of Wt1suppresses FGF and induces BMP signalling.

    • Fariba Jian Motamedi
    • , Danielle A. Badro
    •  & Andreas Schedl

  • Article
    | Open Access

    Parkinson’s disease can be caused by a rare mutation in the protein VPS35, but the mechanism responsible for this is largely unknown. Here, Zavodszky et al.show that this mutation leads to defects in the recruitment of endosomal protein sorting machinery and consequent inhibition of autophagy in cells.

    • Eszter Zavodszky
    • , Matthew N.J. Seaman
    •  & David C. Rubinsztein

  • Article |

    The pRb target E2F1 possesses contradictory activities in promoting proliferation and apoptosis. Here, the authors define a pRb-Skp2-p27-cyclin A-E2F1 survival pathway that can be disrupted to prevent Rb1-deficient tumorigenesis in the pituitary intermediate lobe.

    • Zhonglei Lu
    • , Frederick Bauzon
    •  & Liang Zhu

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