Cell death articles within Nature Cell Biology

Featured

  • News & Views |

    RIPK1 plays a key role in several inflammatory and cell death signalling pathways. Understanding its regulation is pivotal for identifying diseases that might therapeutically benefit from RIPK1 inhibition. Recent studies now show that TBK1 and IKKε constitute a cell death checkpoint that restrains RIPK1 activation.

    • Klaus Heger
    •  & Vishva M. Dixit

  • News & Views |

    Ferroptosis is a regulated non-apoptotic form of cell death and its functional role in tumorigenesis remains elusive. A study now shows that the tumour suppressor BAP1 enhances ferroptosis by modulating expression of the cystine transporter SLC7A11, leading to improved control of tumour growth.

    • Michael P. Murphy

  • Review Article |

    In this Review, Doherty and Baehrecke discuss the multiple roles of autophagy during cell survival and cell death. They cover the interplay between autophagy, apoptosis and necrosis, as well as engulfment and inflammation.

    • Johnna Doherty
    •  & Eric H. Baehrecke

  • News & Views |

    The cytokine tumour necrosis factor (TNF) and the toll-like receptors (TLRs) coordinate immune responses by activating inflammatory transcriptional programs, but these signals can also trigger cell death. Recent studies identify the MAP kinase substrate MK2 as a key player in determining whether cells live or die in response to TNF and TLR signalling.

    • Andrew Oberst

  • Article |

    Dondelinger et al. and Menon et al. show that MAPKAP kinase-2 (MK2) phosphorylates RIPK1 to regulate TNF-mediated cell death as well as RIPK1 signalling in inflammation and bacterial infection.

    • Yves Dondelinger
    • , Tom Delanghe
    •  & Mathieu J. M. Bertrand

  • News & Views |

    Cancer treatments often focus on killing tumour cells through apoptosis, which is thought to typically require mitochondrial outer membrane permeabilization (MOMP) and subsequent caspase activation. A study now shows that MOMP can trigger TNF-dependent, but caspase-independent cell death, suggesting a different approach to improve cancer therapy.

    • Brent E. Fitzwalter
    •  & Andrew Thorburn

  • News & Views |

    Although the mitochondrial inner membrane rhomboid peptidase PARL is known to participate in critical signalling cascades, its role in apoptosis has remained unclear. PARL is now shown to process the mitochondrial pro-apoptotic protein Smac (also known as DIABLO) for its subsequent release into the cytosol where it antagonizes XIAP-mediated caspase inhibition to promote apoptosis.

    • Naotada Ishihara
    •  & Katsuyoshi Mihara

  • News & Views |

    Selective autophagy is essential for maintaining cellular homeostasis under different growth conditions. Huntingtin, mutated versions of which have been implicated in Huntington disease, is now shown to act as a scaffold protein that couples the induction of autophagy and the selective recruitment of cargo into autophagosomes.

    • Amir Gelman
    • , Moran Rawet-Slobodkin
    •  & Zvulun Elazar

  • Article |

    Medina, Ballabio and colleagues report that calcium release from the lysosome stimulates calcineurin, which dephosphorylates and activates TFEB. These findings reveal a central role for calcium signalling in autophagy and lysosome homeostasis.

    • Diego L. Medina
    • , Simone Di Paola
    •  & Andrea Ballabio

  • Article |

    Zhang, Cuervo and colleagues find that Huntingtin (Htt), which is commonly mutated in Huntington disease, regulates selective autophagy. Htt enhances interactions between p62, LC3 and ubiquitylated cargo and derepresses ULK1 kinase activity.

    • Yan-Ning Rui
    • , Zhen Xu
    •  & Sheng Zhang

  • Article |

    Ferroptosis is a form of non-apoptotic cell death with unclear physiological relevance. Conrad and colleagues now report that unrestrained ferroptosis can lead to renal failure. They also identify a small molecule that limits ferroptosis in vivo.

    • Jose Pedro Friedmann Angeli
    • , Manuela Schneider
    •  & Marcus Conrad

  • News & Views |

    Stat3 has been shown to regulate lysosome membrane permeabilization and cell death in vivo during post-lactation mammary gland involution. It is now revealed that Stat3 induces lysosome membrane permeabilization by causing phagocytosis of milk fat globules, which destabilize the lysosome membrane leading to leakage of cathepsin proteases.

    • Shefali Krishna
    •  & Michael Overholtzer

  • News & Views |

    Anti-tubulin drugs are life-saving chemotherapeutics that kill cancer cells by stabilizing or disrupting microtubules. Despite their clinical utility, the molecular mechanisms by which anti-tubulins cause apoptotic cell death remain poorly understood. It is now shown that microtubule disruption can inhibit anti-apoptotic Bcl-2 family proteins through an evolutionarily conserved signalling axis involving DEPDC1 (LET-99 in Caenorhabditis elegans) and JNK.

    • Daniel P. Denning
    •  & Takashi Hirose

  • Article |

    The Raf-1 kinase is important for mitogenic MAPK signalling but also inhibits pro-apoptotic Hippo signalling. Kolch and colleagues have found that the Hippo kinase LATS1 phosphorylates Raf-1 in a feedback regulatory loop to inhibit both pathways, and demonstrate by experiments and modelling that competing protein interaction can form the basis for a switch-like transition between signalling pathways.

    • David Romano
    • , Lan K. Nguyen
    •  & Walter Kolch

  • News & Views |

    Macroautophagy is a key regulator of cellular integrity and viability, but how the process facilitates apoptosis has remained poorly defined. It has now become clear that autophagy degrades the Fap-1 protein phosphatase, a critical negative regulator of apoptotic cell death signalled by the TNF receptor family member, Fas.

    • Sanket Joshi
    •  & Kevin M. Ryan

  • Article |

    Data suggest that autophagy, a process normally associated with cell survival, also promotes cell death, depending on the stimulus or cell type. Thorburn and colleagues find that differences in basal autophagy levels in cells determine survival or death in response to death receptor activation, through modulation of Fap-1 degradation.

    • Jacob M. Gump
    • , Leah Staskiewicz
    •  & Andrew Thorburn

  • News & Views |

    Calcium enters mitochondria through a dedicated channel referred to as the mitochondrial calcium uniporter (MCU), whose molecular identity has long remained elusive. Since the discovery of the gene encoding the MCU protein two years ago, researchers have awaited the generation of a mouse lacking the MCU. These mice are fully viable and show defects limited to performance of high-energy-demanding exercises. Strikingly, no protection against necrosis is observed following ischaemia-reperfusion in the heart.

    • Sébastien Herzig
    • , Kinsey Maundrell
    •  & Jean-Claude Martinou

  • Article |

    Until the recent discovery of the mitochondrial calcium uniporter (MCU), the effect of increases in mitochondrial calcium levels could not be tested in vivo. Finkel and colleagues have knocked out the gene coding for MCU in adult mice, and show that MCU is required for transport of calcium into the mitochondria. They also show that, in its absence, the function of skeletal muscle is altered; however, surprisingly, no effects are observed on the sensitivity to cell-death-inducing agents.

    • Xin Pan
    • , Jie Liu
    •  & Toren Finkel

  • News & Views |

    Autophagy contributes to lipid catabolism through direct mobilization and breakdown of cellular lipid stores. Two recent studies reveal the regulatory mechanisms activated by cells during starvation to ensure that the cellular compartments involved in autophagic lipid catabolism are ready to receive, process and use these lipids. The regulators represent attractive therapeutic targets to help fight lipid-excess-associated diseases.

    • Ana Maria Cuervo

  • Article |

    In the presence of stress stimuli, the endoplasmic reticulum either adapts the protein synthesis or triggers an apoptotic response, but the mechanisms underlying this decision are unknown. Kaufman and colleagues show that the ER stress response factors ATF4 and CHOP increase protein synthesis, which in turn induces oxidative stress and increased ATP consumption, leading to cell death during chronic ER stress.

    • Jaeseok Han
    • , Sung Hoon Back
    •  & Randal J. Kaufman

  • Letter |

    Voinnet and colleagues show that autophagy targets RNAi components DICER and AGO2 for degradation when they are not bound to miRNA. The autophagy receptor NDP52 is required for this homeostatic regulation of the RNAi machinery. The authors also found that autophagy influences the post-translational regulation of DICER mRNA.

    • Derrick Gibbings
    • , Serge Mostowy
    •  & Olivier Voinnet

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