Cell death articles within Nature Communications

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  • Article
    | Open Access

    Ferroptosis is cell death caused by lipid peroxidation and plasma membrane rupture. Here, the authors report an additional role for the lipid flippase SLC47A1 as a regulator of lipid remodeling and survival during ferroptosis, thereby providing a metabolic target for overcoming drug resistance.

    • Zhi Lin
    • , Jiao Liu
    •  & Minghua Yang

  • Article
    | Open Access

    Efferocytosis describes the engulfment and clearance of apoptotic cells by phagocytes. Here the authors identify in primary mouse macrophage WDFY3 as a regulator for efferocytosis, in which c-terminal WDFY3 is sufficient to modulate degradation while full-length WDFY3 is required to modulate the uptake of apoptotic cells.

    • Jianting Shi
    • , Xun Wu
    •  & Hanrui Zhang

  • Article
    | Open Access

    Ferroptosis is a promising therapeutic target for a variety of diseases, but a majority of known ferroptosis inhibitors belong to either antioxidants or iron chelators. Here, the authors discover a new non-classical small molecule inhibitor that is a PHB2 binder and show it ameliorates liver damage in an acute liver injury model.

    • Wei Yang
    • , Bo Mu
    •  & Shengyong Yang

  • Article
    | Open Access

    In situ generated lesion of red blood cells decreases the quality of stored blood and limits its shelf-life. Here, the authors demonstrate that intermittent scavenging of storage lesions using electrostatic interactions by nanofibrous sheets could enhance the quality and shelf-life of stored blood.

    • Subhashini Pandey
    • , Manohar Mahato
    •  & Praveen Kumar Vemula

  • Article
    | Open Access

    The receptor-interacting protein (RIPK1) promotes cell death and contributes to nonalcoholic steatohepatitis pathogenesis. Here the authors report that a SUMO-specific protease, SENP1, deSUMOylates RIPK1 and inhibits cell death in a mouse model of non-alcoholic fatty liver disease.

    • Lingjie Yan
    • , Tao Zhang
    •  & Daichao Xu

  • Article
    | Open Access

    Active regulation of chirality, or handedness, is crucial for life. Here, the authors describe assays to characterise proteome chirality in vivo and show that errors degrade enzyme activity triggering tumour formation and reduced lifespan.

    • Agnes Banreti
    • , Shayon Bhattacharya
    •  & Stéphane Noselli

  • Article
    | Open Access

    Reductive stress, reflected by the elevated intracellular NADH/NAD+ ratio, is associated with multiple human diseases. Here, the authors develop a genetic tool to manipulate the ratios of cellular NADH/NAD+ and NADPH/NADP+, and identify purine biosynthesis as an NADH-sensing pathway to mediate reductive stress.

    • Ronghui Yang
    • , Chuanzhen Yang
    •  & Binghui Li

  • Article
    | Open Access

    Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important regulator of cell death pathways during embryogenesis and in infection/inflammation. Here authors show that tyrosine phosphorylation of RIPK1 by upstream kinases limits systemic inflammation and regulates haematopoietic homeostasis.

    • Hailin Tu
    • , Weihang Xiong
    •  & Xin Lin

  • Article
    | Open Access

    Across phylae, excess manganese disrupts energy metabolism by unclear mechanisms. Here, Diessl et al. report that failure of mitochondrial bioenergetics upon manganese overload is due to mismetallation of a diiron enzyme crucial for CoQ biosynthesis

    • Jutta Diessl
    • , Jens Berndtsson
    •  & Sabrina Büttner

  • Article
    | Open Access

    Immunoglobulin light chain amyloidosis is a lethal hematologic disorder driven by clonal plasma cells producing abnormal light chains that damage healthy tissues. Fraser et al. show that BH3 mimetics, which inhibit pro-survival proteins BCL-2 or MCL-1, can effectively eliminate diseased cells.

    • Cameron S. Fraser
    • , Johan K. E. Spetz
    •  & Kristopher A. Sarosiek

  • Article
    | Open Access

    Protein kinase-mediated phosphorylation plays a critical role in many biological processes. Here the authors develop a trans-omics-based algorithm called Central Kinase Inference to integrate quantitative transcriptomic and phosphoproteomic data, finding that PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.

    • Yangyang Yuan
    • , Chenwei Wang
    •  & Pengyu Huang

  • Article
    | Open Access

    MYC activation can sensitise cells to apoptosis upon glutamine withdrawal. Here the authors show that MYC activation enhances global transcription and translation that creates a metabolic demand, while glutamine limitation causes a metabolic demand and supply imbalance through loss of TCA energetics and thus, sensitises cells to apoptosis.

    • Joy Edwards-Hicks
    • , Huizhong Su
    •  & Andrew J. Finch

  • Article
    | Open Access

    After acute injury, kidneys either successfully repair/regenerate or become fibrotic. Here the authors use scRNA-seq to study adaptive/maladaptive kidney regeneration and identify proinflammatory/fibrotic proximal tubule cells with pharmacologically targetable pyroptosis/ferroptosis signatures.

    • Michael S. Balzer
    • , Tomohito Doke
    •  & Katalin Susztak

  • Article
    | Open Access

    Mitofusins regulate mitochondrial fusion. Here the authors identify small molecules that activate or inhibit mitofusins’ activity and modulate mitochondrial fusion and functionality. Inhibition of mitochondrial fusion promotes minority MOMP, caspase-3/7 activation, and DNA damage.

    • Emmanouil Zacharioudakis
    • , Bogos Agianian
    •  & Evripidis Gavathiotis

  • Article
    | Open Access

    Inducing ferroptosis of tumour cells is a promising therapeutic approach in cancer. Authors show here that on the other hand, cells dying via ferroptosis are less immunogenic than necroptotic cells, they inhibit maturation and antigen cross-presentation of dendritic cells, hence lessen the anti-tumour immune response.

    • Bartosz Wiernicki
    • , Sophia Maschalidi
    •  & Peter Vandenabeele

  • Article
    | Open Access

    Using the Drosophila pupal notum, the authors demonstrate that the disassembly of microtubules by effector caspases initiate cell extrusion independently of actomyosin regulation, thus providing insights into how caspases orchestrate dying epithelial cell expulsion.

    • Alexis Villars
    • , Alexis Matamoro-Vidal
    •  & Romain Levayer

  • Article
    | Open Access

    Fatty acid unsaturation by stearoyl-CoA desaturase 1 (SCD1) protects against cellular stress through unclear mechanisms. Here the authors show 1,2-dioleoyl-sn-glycero-3-phospho-(1’-myo-inositol) is an SCD1-derived signaling lipid that regulates stress-adaption, protects against cell death and promotes proliferation.

    • Maria Thürmer
    • , André Gollowitzer
    •  & Andreas Koeberle

  • Article
    | Open Access

    CD123, the interleukin-3 receptor alpha chain, is aberrantly expressed in acute myeloid leukemia blasts and leukemia stem cells. Here the authors report the design and characterize the anti-tumor activity of allogeneic CD123-targeted CAR-T cells as a therapeutic approach for acute myeloid leukemia.

    • Mayumi Sugita
    • , Roman Galetto
    •  & Monica L. Guzman

  • Article
    | Open Access

    Catalytic iron is associated with intensive care unit mortality and is known to cause free radical-mediated cellular toxicity. Here the authors show that a soluble ferrostatin-analogue (a ferroptosis inhibitor) protects mice from injury and death in experimental iron overload induced and genetic models of organ dysfunction, but not sepsis-induced multiorgan dysfunction.

    • Samya Van Coillie
    • , Emily Van San
    •  & Tom Vanden Berghe

  • Article
    | Open Access

    In this new study the Authors demonstrated that the IGFBP3/TMEM219 pathway is a physiological regulator of pancreatic beta cell homeostasis and it is dysregulated in diabetes. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.

    • Francesca D’Addio
    • , Anna Maestroni
    •  & Paolo Fiorina

  • Article
    | Open Access

    The authors show that the mechanism of BAK activation in mitochondrial apoptosis involves cooperation between direct activation by BH3-only protein BID and BAK autoactivation, providing a unifying basis for BAK triggering by BH3 ligands.

    • Geetika Singh
    • , Cristina D. Guibao
    •  & Tudor Moldoveanu

  • Article
    | Open Access

    Polymyositis (PM) is a chronic inflammatory myopathy characterized by progressive muscle weakness. Here the authors showed that muscle fibers in PM undergo necroptosis and aggravate inflammation via releasing pro-inflammatory molecules such as HMGB1.

    • Mari Kamiya
    • , Fumitaka Mizoguchi
    •  & Shinsuke Yasuda

  • Article
    | Open Access

    During pyroptosis, gasdermin D (GSDMD) forms plasma membrane pores that initiate cell lysis. Here, the authors develop optogenetically activatable human GSDMD to assess GSDMD pore behavior and show that they are dynamic and can close, which can be a pyroptosis regulatory mechanism.

    • Ana Beatriz Santa Cruz Garcia
    • , Kevin P. Schnur
    •  & Gary C. H. Mo

  • Article
    | Open Access

    Pyroptosis, a gasdermin-mediated inflammatory cell death, could be harnessed therapeutically to improve response to cancer immunotherapy. Here the authors report the development of recombinant adeno-associated viruses to deliver the pore-forming N-terminal domain of gasdermin into cancer cells, promoting pyroptosis and anti-tumor immune responses in preclinical cancer models.

    • Yuan Lu
    • , Wenbo He
    •  & Gang Cao

  • Article
    | Open Access

    The pseudokinase MLKL is activated by the upstream kinase RIPK3 in the necroptotic pathway but the structural basis of MLKL activation is not well understood yet. Here, the authors present the crystal structures of the human RIPK3:MLKL complex and human RIPK3 kinase alone, which reveal structural differences between human and murine RIPK3 and they discuss mechanistic implications.

    • Yanxiang Meng
    • , Katherine A. Davies
    •  & James M. Murphy

  • Article
    | Open Access

    The tuberculosis necrotizing toxin (TNT) is the major cytotoxicity factor of M. tuberculosis (Mtb). Mtb possesses five type VII secretion systems (ESX). Pajuelo et al. show that the ESX-4 system is required for TNT secretion and that ESX-2 and ESX-4 systems work in concert with ESX-1 to permeabilize the phagosomal membrane and enable trafficking of TNT into the cytoplasm of macrophages infected with Mtb.

    • David Pajuelo
    • , Uday Tak
    •  & Michael Niederweis

  • Article
    | Open Access

    OTULIN is a deubiquitinase for linear ubiquitin chains. Here the authors show, using genetic mouse models and single-cell RNA-sequencing, that deficiency of OTULIN in keratinocytes causes skin inflammation and verrucous carcinoma via the induction of keratinocyte death, thereby implicating a function of OTULIN in keratinocyte homeostasis.

    • Esther Hoste
    • , Kim Lecomte
    •  & Geert van Loo

  • Article
    | Open Access

    OTULIN is a negative regulator of linear ubiquitination, and its deficiency in human causes multi-organ inflammations including the skin. Here the authors show, by combining various genetic tools with epidermis-specific Otulin knockout mice, that Otulin suppresses skin inflammation predominantly by inhibiting RIPK1-mediated keratinocytes necroptosis.

    • Hannah Schünke
    • , Ulrike Göbel
    •  & Manolis Pasparakis

  • Article
    | Open Access

    During herpesvirus infection, most individuals intrinsically suppress a primary infection and therewith preclude potential damage or neurodegeneration of the CNS. Here, Ames et al. show that Optineurin (OPTN), a conserved autophagy receptor, restricts HSV-1 spread, degrades viral VP16 through autophagy and is neuroprotective against HSV infection in vivo.

    • Joshua Ames
    • , Tejabhiram Yadavalli
    •  & Deepak Shukla

  • Article
    | Open Access

    The unfolded protein response (UPR) promotes cell survival in cancers with hyperactive ER stress response. Here the authors show that CARM1, an arginine methyltransferase, controls the IRE1α/XBP1 pathway of the UPR and the inhibition of this pathway can inhibit growth in CARM1 expressing ovarian cancers.

    • Jianhuang Lin
    • , Heng Liu
    •  & Rugang Zhang

  • Article
    | Open Access

    Cell death is a critical process in health and disease, yet available markers record later stages of cell death once a cell has already begun to decompose. Here the authors show the use of a genetically encoded calcium indicator that demarcates an irreversible stage of cell death earlier than previously possible.

    • Jeremy W. Linsley
    • , Kevan Shah
    •  & Steven Finkbeiner

  • Article
    | Open Access

    Cholesterol metabolism is involved in the progression of aggressive prostate cancer (PCa). Here the authors show that miR-205 downregulation promotes cholesterol synthesis and androgen receptor signalling in PCa through enhancing the expression of the rate-limiting enzyme of cholesterol synthesis, squalene epoxidase.

    • C. Kalogirou
    • , J. Linxweiler
    •  & A. Schulze

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