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  • Review Article |

    Direct reprogramming converts cells from one lineage into cells of another without going through an intermediary pluripotent state. This Review describes our current understanding of the molecular mechanisms underlying direct reprogramming as well as the progress in improving its efficiency and the maturation of reprogrammed cells, and the challenges associated with its translational applications.

    • Haofei Wang
    • , Yuchen Yang
    •  & Li Qian

  • Review Article |

    The majority of mitochondrial proteins are encoded in the nucleus, but mitochondria have an independent protein synthesis machinery that is required for the biogenesis of the respiratory chain. Recent insights into the mechanisms and regulation of mitochondrial protein synthesis have increased our understanding of mitochondrial function and its integration with cell physiology.

    • Eva Kummer
    •  & Nenad Ban

  • Review Article |

    Biomolecular condensates, which form via liquid−liquid phase separation in a tightly regulated manner, have fundamental roles in cellular organization and physiology. Recent studies provide insight into how cellular stress, ageing-related loss of homeostasis and a decline in protein quality control may contribute to the formation of aberrant, disease-causing condensates.

    • Simon Alberti
    •  & Anthony A. Hyman

  • Review Article |

    p38α — the best-characterized member of the p38 kinase family — is a key mediator of cellular stress responses. p38α is activated by a plethora of signals and functions through a multitude of substrates to regulate different cellular behaviours. Understanding context-dependent p38α signalling provides important insights into p38α roles in physiology and pathology.

    • Begoña Canovas
    •  & Angel R. Nebreda

  • Review Article |

    Ferroptosis is a form of regulated cell death driven by iron-dependent phospholipid peroxidation. Since its formal identification in 2012, multiple studies have addressed molecular mechanisms, regulation and functions of ferroptosis, associating this cell death modality with various pathologies, but also proposing its roles in normal physiology and potential for therapeutic targeting.

    • Xuejun Jiang
    • , Brent R. Stockwell
    •  & Marcus Conrad

  • Review Article |

    Tissue morphogenesis is instructed by the interplay of biochemical cues, mechanics and tissue geometry. Conceptually, these instructions can be deployed either deterministically, functioning as a pre-patterned programme for shape changes, or stochastically, whereby the shape emerges in a self-organized fashion. This Review discusses recent insights into how pre-patterned and stochastic tissue shaping are integrated during development.

    • Claudio Collinet
    •  & Thomas Lecuit

  • Review Article |

    Insulin secretion from pancreatic β-cells is potently activated by an increase in glucose after feeding but other dietary components — amino acids, fatty acids, metabolites, α-cell-produced peptides and gastrointestinal tract hormones — further control this response. Deciphering this complex regulation is important to increase our understanding of pancreatic dysfunction in diabetes.

    • Jonathan E. Campbell
    •  & Christopher B. Newgard

  • Review Article |

    Recent studies have provided novel insight into the biogenesis of long non-coding RNAs (lncRNAs) and their specific functions. The functions of lncRNAs vary from transcriptional and post-transcriptional gene regulation to the assembly and function of membraneless nuclear bodies, and are relevant to neuronal disorders, immune responses and cancer.

    • Luisa Statello
    • , Chun-Jie Guo
    •  & Maite Huarte

  • Review Article |

    Nicotinamide adenine dinucleotide (NAD+) is a central redox factor and enzymatic cofactor that functions in a plethora of cellular processes, including metabolic pathways and DNA metabolism, and affects cell fate and function. NAD+ levels gradually decline with age, and therapeutic elevation of NAD+ levels is being trialled for extending human healthspan and lifespan.

    • Anthony J. Covarrubias
    • , Rosalba Perrone
    •  & Eric Verdin

  • Review Article |

    Cellular senescence is characterized by a permanent proliferation arrest and the establishment of a senescence-associated secretory phenotype. This Review discusses the mechanisms of cellular senescence and induction of a senescence-associated secretory phenotype, recent insights into how senescence contributes to ageing, and the potential of senolytic and senomorphic therapies in ageing and associated diseases.

    • Raffaella Di Micco
    • , Valery Krizhanovsky
    •  & Fabrizio d’Adda di Fagagna

  • Review Article |

    Transcript elongation by RNA polymerase II can be perturbed by barriers such as promoter-proximal pausing and nucleosomes and by obstacles such as the replication machinery and DNA lesions. Recent studies revealed how different contexts of RNA polymerase II stalling are distinguished and resolved, and how unresolved stalling can cause genome instability.

    • Melvin Noe Gonzalez
    • , Daniel Blears
    •  & Jesper Q. Svejstrup

  • Review Article |

    Mechanical forces are important regulators of cell function and behaviour. This role is partly achieved through the modulation of cell metabolism, which, reciprocally, affects tissue mechanics. Unravelling the mechanisms of this crosstalk will increase our understanding of how cells interact with their microenvironment.

    • Patrizia Romani
    • , Lorea Valcarcel-Jimenez
    •  & Sirio Dupont

  • Roadmap |

    Biomolecular condensates are membraneless molecular assemblies formed via liquid–liquid phase separation. They have a plethora of roles, ranging from controlling biochemical reactions to regulating cell organization and cell function. This article provides a framework for the study of condensate functions across these cellular length scales, offering to bring new understanding of biological processes.

    • Andrew S. Lyon
    • , William B. Peeples
    •  & Michael K. Rosen

  • Review Article |

    The mitochondrial proteome comprises ~1,000–1,500 nuclear-encoded and mitochondrial-encoded proteins. To ensure proper mitochondrial function, cells use multiple mechanisms of quality control that survey mitochondrial protein biogenesis, import and folding, and allow mitochondria to adapt to the changing needs as well as to respond to stresses that compromise proteostasis.

    • Jiyao Song
    • , Johannes M. Herrmann
    •  & Thomas Becker

  • Review Article |

    Various physiological processes including development and maintenance of epithelia, cell–cell fusion, neuronal function and immune responses rely on the establishment of direct cell–cell contacts. Despite their diversity, the different cell–cell interfaces can be viewed as specialized compartments that perform their distinct functions through common biophysical properties.

    • Brian Belardi
    • , Sungmin Son
    •  & Daniel A. Fletcher