Narendra and Youle review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, highlighting the underlying mechanisms and physiological relevance of the pathway, as well as its role in neuroprotection.

Pluripotent stem cells are being used to generate models of early embryogenesis that are promising for discovery and translational research. To be useful, these models require critical consideration of their level of efficiency and fidelity to natural embryos. Here we propose criteria with which to raise the standards of stem-cell-based embryo models of human embryogenesis.

Man and Kanneganti discuss how pattern-recognition sensors in innate immune cells recognize and respond to cell-death signatures, and highlight molecular targets for potential therapeutic development.

Gasdermins are a family of proteins that form membrane pores and elicit pyroptosis. This Review discusses recent work highlighting their regulation and emerging biological roles, including in non-lethal pore formation and host defence.

Stockhammer, Adarska et al. describe ARF1 compartments as the site of adaptor- and clathrin-dependent post-Golgi sorting. Shedding of ARF1 and maturation into recycling endosomes drives sorting of secretory and endocytic recycling cargo.

Toettcher, McNamara and colleagues use synthetic ‘signal-recording’ gene circuits on mouse gastruloids and find that cell sorting rearranges patchy domains of Wnt activity into a single pole, which defines the gastruloid anterior–posterior axis.

Bose, Rankovic et al. show that a specific RNA–RNA kissing-loop interaction plays a crucial role in driving biomolecular condensation of ribonucleoprotein granules in the Drosophila germline.

Zhao et al. report that the Z compartment protein HERD-1 regulates transgenerational epigenetic inheritance in Caenorhabditis elegans at least in part by preventing the mixing of germ granule condensates.

Yuzhalin et al. report that astrocyte-mediated upregulation of Cdk5 in metastatic breast cancer cells inhibits MHC-I expression on the cell surface, thereby enabling escape from killing by CD8⁺ T cells and facilitating brain metastasis.

Al-Refaie et al. show that fasting induces spatial reorganization of chromatin and formation of chromatin rings in an mTORC1- and RNA Pol I-dependent manner in the C. elegans intestine.

This issue presents a Focus of specially commissioned articles that discuss cell death in its multiple forms, implications for homeostatic physiology and disease and outstanding questions in this expanding field.

Pluripotent stem cells are being used to generate models of early embryogenesis that are promising for discovery and translational research. To be useful, these models require critical consideration of their level of efficiency and fidelity to natural embryos. Here we propose criteria with which to raise the standards of stem-cell-based embryo models of human embryogenesis.