Review Articles

The inner mitochondrial membrane forms cristae, which are crucial for mitochondrial function. This Review explores the protein complexes that regulate cristae dynamics, including remodelling and fusion, and discusses recent structural insights that have increased our understanding of mitochondrial architecture.

The tumour suppressor p53 controls non-apoptotic cell death (NACD) pathways, including ferroptosis, necroptosis and pyroptosis. This Review discusses the roles, mechanisms and physiological settings in which NACDs are regulated by p53, and their potential targeting for the treatment of human diseases.

Coat protein complex II (COPII) subunits assemble to form membrane transport carriers at ER exit sites, thereby concentrating secretory cargoes and facilitating their transport to the Golgi. This Review discusses the mechanisms of coat assembly and disassembly, and cargo recognition by COPII carriers.

DNA end resection is crucial for most DNA double-strand break repair pathways. This Review discusses the molecular mechanisms of end resection and its regulation, focusing on the roles of post-translational modifications throughout the cell cycle and in response to DNA damage.

Activation of gasdermins (GSDMs) in response to infection or cell damage triggers membrane pore formation, leading to pyroptotic cell death. This Review discusses recent molecular and structural insights into the regulation of GSDMs and explores their physiological roles and involvement in inflammatory diseases.

Changes in nuclear and genome organization promote the repair of DNA double-strand breaks and genome stability. Processes that are involved include the modulation of chromatin state, condensates of repair proteins and cytoskeleton reorganization. The reshaping of the nucleus and genome is commonly altered in cancer and during ageing, which could be targeted to provide new therapeutic opportunities.

The Notch pathway regulates many developmental and homeostatic processes in animals. This Review discusses how different modes of Notch signalling can have different functional outcomes, and how their dysregulation is associated with cancer states.

CRISPR–Cas-mediated genome, epigenome and transcriptome engineering in crops is crucial as the human population grows and climate deteriorates. This Review discusses new CRISPR–Cas tools for precise engineering, and their uses in improving crop traits such as yield and tolerance to climate stresses.

Insulin and insulin-like growth factor (IGF) signalling regulates metabolism, cell growth and proliferation and diverse cell-specific processes. This Review discusses recent structural insights into insulin–receptor and IGF–receptor binding and activation, regulation of insulin and IGF signalling and new agonists with therapeutic potential.

Adult stem cells self-renew and differentiate to build, maintain and repair tissues. This Review discusses recent insights into the contribution of mechanical forces produced by epithelial stem cell activity in building surrounding tissues, and the roles of stem cell niche mechanics disruption in cancer.

Endothelial cells (ECs) undergo organ-specific specialization, driven by microenvironmental cues, to form patterned vascular networks. This article discusses mechanisms driving vascular inter-organ and intra-organ EC heterogeneity, crosstalk between ECs and neighbouring cells, and the therapeutic potential of engineering ECs.

Mitochondria rapidly take up calcium (Ca²⁺) from the cytoplasm and neighbouring organelles upon an increase in local and global calcium levels, thereby stimulating metabolism and regulating processes that are sensitive to Ca²⁺. This Review discusses mitochondrial calcium trafficking and its dysregulation in disease.

Many new small RNA species and their derived fragments have been recently identified in animals. This Review discusses the biogenesis and functions of both structural small RNAs, such as tRNAs and small nuclear RNAs (snRNAs), and of regulatory small RNAs such as microRNAs and PIWI-interacting RNAs (piRNAs).

Wnt–β-catenin signalling regulates stem cell renewal, development and tissue homeostasis. In this Review, the authors examine recent findings concerning Wnt protein production, receptor activation and intracellular signalling, focusing on the regulation of the β-catenin destruction complex.

Communication between the circadian clocks of different cell and tissue types supports the daily rhythms of homeostatic processes that maintain bodily health. Ageing leads to a decline in this complex communication network to the detriment of these daily homeostatic rhythms. This Review discusses clock communication pathways in the healthy versus aged state and explores the potential of modulating these communication pathways to slow circadian rhythm decline with ageing.

MicroRNAs (miRNAs) are small non-coding RNAs that induce RNA silencing. Advances in high-throughput and structural studies have provided new insights into animal miRNA biogenesis mediated by RNA–protein interactions, miRNA tailing (uridylation or adenylation) and RNA modifications, and have increased our understanding of miRNA target recognition and target-directed miRNA decay.

During mammalian embryogenesis, extraembryonic tissues are required for the patterning and morphogenesis of the embryo. This Review discusses how signalling networks and epigenetic modifications regulate the development and function of the different extraembryonic tissues during implantation, axis specification and gastrulation.

Telomere dysfunction, usually owing to shortening, activates cellular senescence and can contribute to age-associated diseases and cancer. Mouse models are crucial for telomere research, but human and mouse telomeres have key differences. This Review discusses telomere maintenance and damage, and recent efforts to generate ‘humanized’-telomere mouse models.

Intraflagellar transport (IFT) ensures delivery of selected proteins into cilia. The IFT protein complexes IFT-A and IFT-B polymerize at the base of the cilium to form an anterograde train that facilitates cargo import, whereas remodelling into a retrograde train at the ciliary tip enables cargo export.

Transcriptional condensates, which are formed through dynamic multivalent interactions between proteins, RNA and chromatin, regulate transcription by compartmentalizing its machinery in the crowded nuclear environment. These condensates regulate animal and plant development, cell signalling and responses to the environment, and they are dysregulated in developmental disorders, cancer and neurodegeneration.