UFM1 is a ubiquitin-like modifier (UBL) that is important to maintain homeostasis at the endoplasmic reticulum and mutations in this pathway lead to neurodevelopmental disorders and multiple pathologies. Being the most recently discovered UBL, we are only now beginning to understand the mechanisms and functions of this enigmatic modifier. In this review, we provide a comprehensive guide to the mechanisms and biological function of protein UFMylation.

John F. Cryan is the Principal Investigator at the APC Microbiome Ireland Institute at the University College of Cork, Ireland. His lab focuses on determining the impact of the gut microbiota on human brain and behaviour. Over the years, John has received many honours and accolades in recognition of his significant contributions to understanding the brain–gut–microbiome axis. In this interview, he outlines how he became interested in the role of the microbiome in brain development and disease, provides advice to budding scientists and highlights the broader public health implications of his research.

Cellular senescence is frequently induced in response to ageing and stress. Yet, studies have also uncovered beneficial functions in development, repair and regeneration. Therefore, timely and controlled induction of senescence can be beneficial, while misregulation of the senescence program contributes to disease and ageing. Here, we discuss recent studies that implicate ectopic senescence in neurodevelopmental defects and highlight how the examination of senescence in other birth defects is warranted.

The soil bacterium Chitinophaga pinensis secretes a cocktail of enzymes that can deconstruct complex fungal cell walls, releasing sugars to be used for metabolism. Three such enzymes, from different glycoside hydrolase families, are characterised in this study. They use different strategies to interact with fungal β-1,6-glucan (pustulan), leading to different efficiencies in polysaccharide breakdown. This work shows how diverse enzymatic approaches can be used to target a recalcitrant substrate.

Metabolic pathways are regulated through the formation of metabolons. Using a two-hybrid approach, we demonstrate a dense protein interaction network among the enzymes of the E. coli de novo purine nucleotide biosynthesis. Alterations of this network through mutations impact purine nucleotide pools and bacterial fitness. Our data suggest that the bacterial de novo purine nucleotide biosynthesis enzymes assemble in a supramolecular complex and proper interactions within it contribute to bacterial fitness.

The microenvironment of three-dimensional (3D) cell culture systems closely mimics the in vivo tumour conditions. Cancer cells in 3D platforms secrete a plethora of matrix effectors in the provisional matrix often in higher bioavailability compared with two-dimensional (2D) cell cultures. The exploration of the 3D matrix architectures in advanced cell culture platforms generated through cutting-edge technologies may fill the gap between preclinical cancer research and applied cancer therapeutics.

Cellular senescence, a critical hallmark of ageing, has been shown to drive many age-associated chronic diseases. Senescent cells (SnCs) up-regulate pathways associated with evasion of apoptosis, survival, senescence-associated secretory phenotype (SASP) development and others that are targeted using senotherapeutics. Senotherapeutics selectively target SnCs for their clearance (senolytics) or suppression of their SASP (senomorphics). Many studies have demonstrated the benefit of senotherapeutic treatment for the extension of health and lifespan.

The mechanistic basis for the mitochondrial permeability transition (an inner membrane permeability increase that is a causative event in cell death) has puzzled mitochondrial research for 70 years. Here, we review the field and discuss recent evidence on how a Ca²⁺-dependent conformational change of F-ATP synthase and of adenine nucleotide translocator may transform these energy-conserving devices into energy-dissipating multiconductance channels causing the permeability transition.

IDO1 has a complex functional dynamics capable of fulfilling distinct environmental needs. Besides its catalytic activity degrading tryptophan, IDO1 performs a non-enzymic function that, via activation of SHP1/SHP2 and noncanonical NF-κB, reprograms the expression profile of dendritic cells (DCs) towards a long-term immunoregulatory phenotype. The distinct functions occur either in cytosol (enzymic) or in early endosomes (EE; non-enzymic). In inflammatory conditions, IDO1 is shut down by SOCS3-mediated proteasomal degradation, and an immunostimulatory program is acquired by the DCs.

In this review, nuclear speckles (NS) are revisited in the light of most recent findings about the composition of NS, the role of NS in gene expression regulation and genome architecture, and the evolutionary origins of NS. The long road to understanding the function of NS is also discussed based on these new connections to gene expression regulation and molecular origins of NS. Created with BioRender.com.

With a genetic entry point and new technologies, we are beginning to define functions related to mucin-type O-glycosylation. This includes protection from proteolytic cleavage, modulation of receptor functions, homing and modulation of immune cells, and functions in cell adhesion, metabolism, and host–microbiome interactions. This review presents the achievements and promises in O-GalNAc glycobiology driven by technological advances in analytical methods, genetic engineering, and systems biology.

Migrasomes are newly found organelles produced by migrating cells and grow on retraction fibers trailing behind the cells. Migrasomes are produced as a result of tetraspanin-enriched macrodomain accumulation and could be released into the extracellular matrix or engulfed by other cells. Migrasomes could act as carriers of mRNA, protein, or damaged mitochondria, or as chemoattractive sources.

Peptidoglycan cross-linking enzymes LD-transpeptidases (LDTs) have kept an aura of mystery for a long time. However, a number of recent reports have linked the activity of LDTs to cell wall adaptation to stress including β-lactam antibiotics, outer membrane stability, and toxin delivery. Critically, in some bacteria, LDT activity has a major—even essential—role in PG biosynthesis. In this review, we discuss general and species-specific functions enabled by LD cross-links.

The article talks about the primacy of the Michaelis–Menten equation as a framework for the quantitative understanding of enzyme kinetics. It dwells upon the mathematical elegance of and the assumptions that went into framing the equation. Further, it traces the history of the equation and the growth of the field beyond it. The image shows an artistic rendering of the crowded interiors of a cell and the equation dictating how macromolecular interactions of catalytic nature happen.