Browse Articles

Translation is controlled mainly during its initiation. Recent studies in yeast and mammals provide new insights into the mechanism of translation initiation regulation in health and in various diseases, and open avenues for the development of innovative therapies targeting the translation machinery.

Lysosomes orchestrate key cellular functions such as nutrient sensing, degradation of macromolecules and stress adaptation. This Review discusses the integration of signalling pathways at the lysosome and highlights the interaction of lysosomes with other organelles and mechanisms that ensure lysosome homeostasis.

Florian Heyd describes a paper that pointed towards alternative splicing as a driver of human cognitive abilities.

In this Tools of the Trade article, Manuela Richter (Dumont lab) describes a method to probe mechanisms of cytoskeletal network re-organization that uses a targeted laser to both trigger network remodelling and track network dynamics.

Intrinsically disordered regions of proteins lack a defined 3D structure and exist in a collection of interconverting conformations. Recent work is shedding light on how — through their conformational malleability and adaptability — intrinsically disordered regions extend the repertoire of macromolecular interactions in the cell and contribute to key cellular functions.

Emily Wong describes a study that provided a quantitative methodology for analyzing ChIP experiments and shifted our understanding of the functionality of transcription factors.

In this Tools of the Trade article, Bohan Zhang (Gladyshev lab) discusses how the use of extended heterochronic parabiosis in mice (surgical connection between circulatory systems for an extended period), followed by detachment, can shed light on potential mechanisms that reverse mammalian ageing.

Yu et al. identify senescent cells as important players in the regeneration of complex structures.

The regenerative abilities of mammalian hair follicles are facilitated by the proliferation of hair follicle stem cells (HFSCs), which reside in specialized niches within the skin. Recent studies shed light on how local signals and systemic inputs from the body and the environment regulate HFSC function.

Human endogenous retroviruses (HERVs) are relics of ancient retroviral infections, which provide coding and non-coding sequences to the human genome. Emerging evidence reveals how HERVs contribute to immune responses and embryogenesis and how infections and mutations can dysregulate them and contribute to neurodegeneration, inflammation and oncogenesis.

Phosphorylation of the mitochondrial DNA (mtDNA) maintenance factor TFAM during spermatogenesis prevents its import into mitochondria, resulting in elimination of paternal mtDNA and leading to maternal inheritance.

Ernst and Renne highlight two papers, one that discovered and another that structurally defined the ER–mitochondria encounter structure (ERMES) that facilitates the exchange of lipids between the ER and mitochondria.

Eukaryotic membrane fusion is hindered by energy barriers and often requires soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) to facilitate formation of a fusion pore. Recent studies describe SNARE activity along the fusion pathway and shed light on the regulation of SNARE complex assembly.

Embedded within the complexity of biological systems lies a formidable task: deciphering the intricate architecture of macromolecules. In this Viewpoint, a panel of experts discuss the key challenges and opportunities of macromolecular structure determination, highlighting the crucial synergy between empirical experimentation and artificial intelligence-based techniques in unravelling these complexities.

In this Tools of the Trade article, Christine Lim and Alicia González Díaz (Vendruscolo lab) describe a pipeline for the identification and characterization of proteins whose phase separation is altered in disease.

mTOR inhibition by deprivation of the amino acids Tyr, Trp and Phe promotes the translocation of the 26S proteasome from the nucleus to the cytosol, which is required for stress tolerance and cell survival.

Sarkar et al. identify a feedback loop between the methyltransferase SETDB1 and nuclear pore complexes that ensures silencing of early-oogenesis genes as oocyte specification progresses.

Targeted editing of mitochondrial and chloroplast genomes has therapeutic, agricultural and environmental potential, but it is challenging owing to inability of transfecting (guide) RNA into the organelles. Recent designs of protein-only, programmable base editors open promising avenues for organellar DNA editing in cell lines, animals and plants.

A unique feature of mitochondrial DNA function is the coupling of initiation of transcription with that of replication. Tan et al. discuss the choice between initiation of either process, and how mitochondrial DNA packaging into nucleoids controls its accessibility and function in human cells.

Iron homeostasis in animals is tightly controlled, and numerous cellular pathways regulate iron uptake, storage, metabolism and secretion. Recent findings provide new insights into the sensory systems that fine-tune iron homeostasis and explain how cellular and systemic iron fluxes intersect.