Featured
-
-
Article
| Open Access
Substrate-induced condensation activates plant TIR domain proteins
Binding of the substrates NAD+ and ATP to the plant Toll/interleukin-1 receptor (TIR) domain proteins induces phase separation and, thereby, activation of TIR enzymatic and immune signalling activity.
- Wen Song
- , Li Liu
- & Jijie Chai
-
Article |
7-Dehydrocholesterol is an endogenous suppressor of ferroptosis
Proferroptotic activity of 7-dehydrocholesterol reductase is shown along with an unexpected prosurvival function of its substrate, 7-dehydrocholesterol, indicating a cell-intrinsic mechanism that could be used by cancer cells to protect phospholipids from oxidative damage and escape ferroptosis.
- Florencio Porto Freitas
- , Hamed Alborzinia
- & José Pedro Friedmann Angeli
-
Article |
7-Dehydrocholesterol dictates ferroptosis sensitivity
7-Dehydrocholesterol (7-DHC) is a natural anti-ferroptotic metabolite and pharmacological manipulation of 7-DHC levels shows promise as a therapeutic strategy for cancer and ischaemia–reperfusion injury.
- Yaxu Li
- , Qiao Ran
- & Ping Wang
-
Article
| Open Access
An extra-erythrocyte role of haemoglobin body in chondrocyte hypoxia adaption
Haemoglobin produced by chondrocytes forms eosin-positive haemoglobin bodies in their cytoplasm, and deletion of these bodies causes severe hypoxia.
- Feng Zhang
- , Bo Zhang
- & Qiang Sun
-
Matters Arising |
Reply to: DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition
- Chao Mao
- , Xiaoguang Liu
- & Boyi Gan
-
Matters Arising |
DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition
- Eikan Mishima
- , Toshitaka Nakamura
- & Marcus Conrad
-
Article
| Open Access
Phase separation of FSP1 promotes ferroptosis
An inhibitor of the ferroptosis-suppressing FSP1 induces phase separation of FSP1, thereby impairing its function and reducing tumour growth.
- Toshitaka Nakamura
- , Clara Hipp
- & Marcus Conrad
-
Article
| Open Access
Structural basis of NINJ1-mediated plasma membrane rupture in cell death
Structural, biochemical and mutagenesis studies indicate that, in dying cells, the membrane protein NINJ1 assembles into filaments, disrupting the cell membrane.
- Morris Degen
- , José Carlos Santos
- & Sebastian Hiller
-
Article
| Open Access
Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury
A monoclonal antibody that binds NINJ1 and inhibits NINJ1 oligomerization prevents plasma membrane rupture in dying cells, resulting in decreased inflammation of surrounding tissue in mice.
- Nobuhiko Kayagaki
- , Irma B. Stowe
- & Vishva M. Dixit
-
Article |
Norovirus MLKL-like protein initiates cell death to induce viral egress
The murine norovirus NTPase NS3 induces mitochondrial disruption, resulting in cell death, which is required for viral egress.
- Guoxun Wang
- , Di Zhang
- & Tiffany A. Reese
-
Article
| Open Access
Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis
Dysfunctional telomeres activate innate immune responses through mitochondrial TERRA–ZBP1 complexes to eliminate cells that are destined for neoplastic transformation.
- Joe Nassour
- , Lucia Gutierrez Aguiar
- & Jan Karlseder
-
Article |
The γδ IEL effector API5 masks genetic susceptibility to Paneth cell death
Intraepithelial lymphocytes expressing γ and δ T cell receptor subunits protect Paneth cells from cell death caused by viral infection or Crohn's disease.
- Yu Matsuzawa-Ishimoto
- , Xiaomin Yao
- & Ken Cadwell
-
Article
| Open Access
A non-canonical vitamin K cycle is a potent ferroptosis suppressor
Biochemical and lipidomic analyses identify an anti-ferroptotic function of vitamin K and reveal ferroptosis suppressor protein 1 (FSP1) as the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle.
- Eikan Mishima
- , Junya Ito
- & Marcus Conrad
-
Article |
Caspase-7 activates ASM to repair gasdermin and perforin pores
Caspase-7 cleaves and activates acid sphingomyelinase (ASM), which promotes the repair of gasdermin pores and thereby delays pore-driven lysis to allow other processes such as extrusion or apoptosis to occur before cell death.
- Kengo Nozaki
- , Vivien I. Maltez
- & Edward A. Miao
-
Article |
Targeting SLC7A11 improves efferocytosis by dendritic cells and wound healing in diabetes
Transcriptomic, genetic and pharmacological analysis identifies SLC7A11 as an inhibitor of efferocytosis in dendritic cells, and increased expression of this protein may cause slower wound healing in diabetes.
- Sophia Maschalidi
- , Parul Mehrotra
- & Kodi S. Ravichandran
-
Article |
DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer
DHO dehydrogenase regulates ferroptosis by preventing mitochondrial lipid peroxidation and its inhibition suppresses growth in tumours with low levels of GPX4.
- Chao Mao
- , Xiaoguang Liu
- & Boyi Gan
-
Article |
Replication stress promotes cell elimination by extrusion
A cell-cycle checkpoint triggers the extrusion of both nematode and mammalian cells experiencing replication stress.
- Vivek K. Dwivedi
- , Carlos Pardo-Pastor
- & H. Robert Horvitz
-
Article |
NINJ1 mediates plasma membrane rupture during lytic cell death
The small transmembrane protein NINJ1 promotes plasma membrane rupture in lytic cell death associated with pyroptosis, necrosis and apoptosis.
- Nobuhiko Kayagaki
- , Opher S. Kornfeld
- & Vishva M. Dixit
-
Article |
Plasticity of ether lipids promotes ferroptosis susceptibility and evasion
The cellular organelles peroxisomes contribute to the sensitivity of cells to ferroptosis by synthesizing polyunsaturated ether phospholipids, and changes in the abundances of these lipids are associated with altered sensitivity to ferroptosis during cell-state transitions.
- Yilong Zou
- , Whitney S. Henry
- & Stuart L. Schreiber
-
Article |
Separase-triggered apoptosis enforces minimal length of mitosis
If early mitosis is too short, separase induces apoptosis by cleaving MCL2 and BCL-XL, thereby eliminating cells that are prone to chromosome missegregation.
- Susanne Hellmuth
- & Olaf Stemmann
-
Article |
Gut stem cell necroptosis by genome instability triggers bowel inflammation
In mouse models of bowel inflammation, depletion of the SETDB1 histone methyltransferase leads to genome instability, which releases repression of endogenous retroviruses that triggers ZBP1-dependent necroptosis and inflammation in gut.
- Ruicong Wang
- , Hongda Li
- & Wei Mo
-
Article |
Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease
Heterozygous mutateons in the caspase-8 cleavage site of RIPK1 cause a range of autoinflammatory symptoms in humans, and caspase-8 cleavage of RIPK1 in a mouse model limits TNF-induced cell death and inflammation.
- Najoua Lalaoui
- , Steven E. Boyden
- & John Silke
-
Article |
A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1
A dominantly inherited human autoinflammatory disease caused by mutations in RIPK1 is identified, and RIPK1 mutations that prevent caspase-8 cleavage sensitize cells to apoptosis, necroptosis and inflammation.
- Panfeng Tao
- , Jinqiao Sun
- & Qing Zhou
-
Article |
FSP1 is a glutathione-independent ferroptosis suppressor
In the absence of GPX4, FSP1 regenerates ubiquinol from the oxidized form, ubiquinone, using NAD(P)H and suppresses phospholipid peroxidation and ferroptosis in cells.
- Sebastian Doll
- , Florencio Porto Freitas
- & Marcus Conrad
-
Article |
The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
A synthetic lethal CRISPR–Cas9 screen identifies ferroptosis suppressor protein 1 as a key ferroptosis-resistance factor, the expression of which correlates with ferroptosis resistance in hundreds of cancer cell lines.
- Kirill Bersuker
- , Joseph M. Hendricks
- & James A. Olzmann
-
Letter |
Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death
Histone H4 is released from neutrophil extracellular traps and induces membrane lysis in vascular smooth muscle cells, leading to the destabilization of atherosclerotic plaques.
- Carlos Silvestre-Roig
- , Quinte Braster
- & Oliver Soehnlein
-
Letter |
CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
Interferon-γ induces ferroptotic cell death in tumours by suppressing cystine uptake and promoting lipid peroxidation.
- Weimin Wang
- , Michael Green
- & Weiping Zou
-
Article |
Pyramidal cell regulation of interneuron survival sculpts cortical networks
Excitatory input onto inhibitory interneurons in the developing mouse cortex acts through PTEN to protect interneurons from cell death and thus regulate the balance between excitation and inhibition.
- Fong Kuan Wong
- , Kinga Bercsenyi
- & Oscar Marín
-
Letter |
LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis
The HOIL-1 component of the LUBAC ubiquitin ligase complex is required for LUBAC activity, which prevents lethality during embryogenesis by preventing aberrant TNFR1-mediated endothelial cell death and RIPK1-mediated defects in haematopoiesis.
- Nieves Peltzer
- , Maurice Darding
- & Henning Walczak
-
Letter |
Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition
Cancer persister cells, which survive cytotoxic treatments, are shown to be sensitive to inhibition of the lipid hydroperoxidase GPX4.
- Matthew J. Hangauer
- , Vasanthi S. Viswanathan
- & Michael T. McManus
-
Letter |
Cysteine protease cathepsin B mediates radiation-induced bystander effects
The cysteine protease CPR-4, a cathepsin B homologue, is identified as a radiation-induced bystander effect (RIBE) factor in nematodes in response to ultraviolet or ionizing radiation, and causes inhibition of cell death and increased embryonic lethality.
- Yu Peng
- , Man Zhang
- & Ding Xue
-
Letter |
The metabolic function of cyclin D3–CDK6 kinase in cancer cell survival
The cyclin D3–CDK6 kinase complex, which is overactive in some cancers, inhibits two key glycolysis enzymes and thereby enhances the levels of antioxidants in cells, promoting tumour cell survival.
- Haizhen Wang
- , Brandon N. Nicolay
- & Piotr Sicinski
-
Letter |
Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin
Chemotherapy drugs can cause pyroptotic cell death by activating caspase-3 to cleave gasdermin E, potentially contributing to their toxicity and adverse effects.
- Yupeng Wang
- , Wenqing Gao
- & Feng Shao
-
Letter |
The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability
Conditional deletion of the mitochondrial Na+/Ca2+ exchanger NCLX in adult mouse hearts causes sudden death due to mitochondrial calcium overload, whereas its overexpression limits cell death elicited by ischaemia reperfusion injury and heart failure.
- Timothy S. Luongo
- , Jonathan P. Lambert
- & John W. Elrod
-
Letter |
Mechanical stretch triggers rapid epithelial cell division through Piezo1
The stretch-activated channel Piezo1 controls homeostatic epithelial cell numbers by activating cells to divide rapidly when under stretch strain from low density, and by activating cells to extrude and die when cells are under crowding strain.
- S. A. Gudipaty
- , J. Lindblom
- & J. Rosenblatt
-
Letter |
The ligand Sas and its receptor PTP10D drive tumour-suppressive cell competition
Wild-type Drosophila epithelial cells outcompete proto-oncogenic cells through translocation of the ligand Sas to the wild-type–tumour cell interface, where it binds the PTP10D receptor of the tumour cell, initiating pro-apoptotic signalling.
- Masatoshi Yamamoto
- , Shizue Ohsawa
- & Tatsushi Igaki
-
Letter |
Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis
Human and murine tumour cells induce programmed necrosis (necroptosis) of endothelial cells, which promotes tumour cell extravasation and metastasis.
- Boris Strilic
- , Lida Yang
- & Stefan Offermanns
-
Letter |
In situ structural analysis of the human nuclear pore complex
The most comprehensive architectural model to date of the nuclear pore complex reveals previously unknown local interactions, and a role for nucleoporin 358 in Y-complex oligomerization.
- Alexander von Appen
- , Jan Kosinski
- & Martin Beck
-
Letter |
A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death
A new pathway of mitochondria-mediated cell death termed mitochondrial precursor over-accumulation stress (mPOS) is identified that could explain the link between mitochondrial dysfunction and misfolding of cytosolic proteins during ageing and disease; the pathway is triggered not only by mutations affecting the core protein import machineries, but also by conditions that interfere with mitochondrial inner membrane integrity and function, and a large network of genes that suppress mPOS in favour of cell survival is also identified.
- Xiaowen Wang
- & Xin Jie Chen
-
Letter |
Cell death during crisis is mediated by mitotic telomere deprotection
Cells that bypass senescence in the absence of the p53 tumour suppressor protein have shortened telomeres that undergo fusion, and these fusions trigger mitotic arrest and cell death in crisis.
- Makoto T. Hayashi
- , Anthony J. Cesare
- & Jan Karlseder
-
Article |
Ferroptosis as a p53-mediated activity during tumour suppression
p53 suppresses expression of SLC7A11, a key component of the cystine/glutamate amino acid transport machinery, leading to inhibition of cystine uptake and promoting ferroptosis, an iron-dependent form of cell death.
- Le Jiang
- , Ning Kon
- & Wei Gu
-
Letter |
Apico-basal forces exerted by apoptotic cells drive epithelium folding
Apoptotic cell death is required for morphogenesis of the developing leg joint of fruitflies; using this model system, the authors show here that within apoptotic cells a transient pulling force exerted through a highly dynamic apico-basal myosin II cable-like structure acts as a mechanical signal to increase tissue tension and modify tissue shape.
- Bruno Monier
- , Melanie Gettings
- & Magali Suzanne
-
Letter |
EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway
Unlike the limited post-injury neuronal regeneration in humans, severed axons in C. elegans can regenerate through a cellular fusion mechanism; this study identifies the molecular basis for this process which includes phosphatidylserine recognition and a role for specific molecules that also act in apoptosis.
- Brent Neumann
- , Sean Coakley
- & Massimo A. Hilliard
-
Letter |
RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis
This study provides evidence for a critical role of RIPK1 in suppressing caspase-8-mediated cell death and maintaining intestinal homeostasis independently of its kinase activity.
- Nozomi Takahashi
- , Lars Vereecke
- & Peter Vandenabeele
-
Article |
Unexpected link between an antibiotic, pannexin channels and apoptosis
The pannexin 1 channel on the plasma membrane of apoptotic cells mediates the release of find-me molecular signals to attract phagocytic cells for clearance of the apoptotic cells; here the quinolone antibiotic trovafloxacin is identified as a direct inhibitor of pannexin 1, which results in dysregulated fragmentation of apoptotic cells and may partly explain quinolone toxicity.
- Ivan K. H. Poon
- , Yu-Hsin Chiu
- & Kodi S. Ravichandran
-
Brief Communications Arising |
Is SIRT2 required for necroptosis?
- Kim Newton
- , Joanne M. Hildebrand
- & John Silke
-
Letter |
Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains
Several death-domain-containing proteins are directly inactivated by the enteropathogenic Escherichia coli type III secretion system effector NleB; NleB functions as an N-acetylglucosamine transferase that modifies a conserved death domain arginine residue, blocking the receptor–adapter interaction.
- Shan Li
- , Li Zhang
- & Feng Shao
-
Letter |
An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways
Removal of cells during development in Caenorhabditis elegans requires the precise execution of cell-death programs, which can include both caspase-dependent and -independent pathways; here it is shown that a single upstream transcription factor can drive both, in parallel, to destroy a single cell.
- Takashi Hirose
- & H. Robert Horvitz
-
Letter |
Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion
The apoptotic event of phosphatidylserine exposure and its recognition by the receptor BAI1 has an unexpected new role as a signal enhancing mouse myoblast fusion, an insight with relevance to some congenital muscle diseases and muscle injury treatments.
- Amelia E. Hochreiter-Hufford
- , Chang Sup Lee
- & Kodi S. Ravichandran
Brain endothelial GSDMD activation mediates inflammatory BBB breakdown