Caspases cleave hundreds of substrates in both lethal and non-lethal scenarios. However, physiological consequences of substrate cleavage are poorly described. Here, Natsuki Shinoda, Masayuki Miura and colleagues found that caspases cleave Drosophila BubR1, a spindle assembly checkpoint component. They showed that Drice, but not Dcp-1, is in proximity to BubR1, suggesting that protein proximity facilitates substrate preference. The cleaved fragments displayed altered subcellular localization and protein–protein interactions. Flies harboring cleavage-resistant BubR1 showed longer duration of BubR1 localization to the kinetochore, as well as extended lifespan. In conclusion, the caspase-mediated cleavage of BubR1 limits spindle assembly checkpoint and organismal lifespan.

Highly efficient CRISPR/Cas9 genome editing in Caenorhabditis elegans has been facilitated by using single-stranded oligonucleotide donors as repair templates. However, insertion of larger sequences remains challenging. Here, Matthew Eroglu, Bin Yu and Brent Derry simplified the generation of long ssDNA as donors in CRISPR/Cas9. High ssDNA yields are rapidly generated using a standard PCR followed by an enzymatic digest with lambda exonuclease. The insertion frequency for these long ssDNA donors is remarkably higher than dsDNA. This can be leveraged to simultaneously generate multiple large insertions and successful edits. This approach enables highly efficient insertion of longer sequences using CRISPR/Cas9 in C. elegans.

The field of enzymology has witnessed landmark developments that have led to its improved understanding at the molecular level and to the discovery of complex relationships between enzyme structures, catalytic mechanisms and biological function. How enzymes are regulated at the gene and post-translational levels and how catalytic activity is controlled are topical areas of the study. Here, Nigel Scrutton introduces The FEBS Journal's Focus Issue on Enzymes, which features breaking science and informative reviews, as well as personal reflections, and illustrates the breadth and importance of contemporary molecular enzymology research.

MIR210HG promotes hypoxia-inducible factor1α (HIF1α) expression via a positive feedback loop. Under hypoxic condition, MIR210HG is rapidly induced and promotes HIF1α through competitively binding to miR-93-5p that degrades HIF1α.

Notch signalling is an evolutionarily conserved pathway that plays a fundamental role in various developmental events. Involvement of the same pathway in several diverse cellular processes is only possible because of the complex regulatory mechanisms of the pathway. In this review, we provide an overview of the mechanism and regulation of the Notch signalling pathway along with its multifaceted functions in different aspects of development and disease.

The development of broadly neutralizing antibodies (BNAbs) against β-coronavirus (βCoV) is important for developing variant-proof therapeutics and vaccines. 1249A8 is a BNAb that targets the stem helix (SH) of βCoV spike proteins. Crystal structure analysis of the 1249A8/MERS-CoV SH complex, and comparisons with other SH-targeting BNAbs, identifies key molecular features of this antibody class that are required for broad-spectrum neutralization of SARS-CoV-1, SARS-CoV-2, and MERS-CoV.

Glycosylation is one of the most common post-translational modifications in nature. Yet, its impact on the enzyme structure–function relationship is limited. Using a combination of experimental and computational modelling, we found that the haem-enzyme horseradish peroxidase becomes more rigid on glycosylation. Rather than increased rigidity impeding catalysis as per the classic ‘activity-stability trade-off’ idea, glycosylation increases turnover by 10-fold and makes the enzyme more stable.

Some of the roles of lysosome membrane proteins in autophagy, with a focus on their roles in vesicular nucleation, vesicular elongation and completion, fusion of autophagosomes and lysosomes, degradation, and their extensive association with related diseases.

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.

The inner blood–retina barrier (iBRB) refers to the properties of endothelial cells associated with the blood vessels of the inner retina. These cells strictly regulate entry and exit from the retina and perturbations in their function have detrimental effects on vision and lead to conditions such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). This review provides a succinct overview of BRB breakdown-associated retinal conditions and the putative underlying mechanisms of disease.

Mitochondria play a central role in the development of cellular senescence. Senescence is characterized by several mitochondrial functional changes such as a decrease in OXPHOS, reduced levels of NAD⁺ and ATP, and accumulation of TCA cycle metabolites, DAMPs, and ROS. Here, we provide an overview of the recent findings demonstrating how these mitochondrial changes can contribute to the senescence-associated growth arrest and the SASP.

Nrf2 activates different cellular mechanisms in response to ischemia-reperfusion (IR) injury in liver. IR is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, ROS generation leads oxidative stress, inflammation and mitochondrial dysfunction. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense and help to promote hepatic recovery during IR.

Alzheimer’s disease (AD) is a neurodegenerative disease with multifactorial etiology, intersecting risk factors, and a lack of disease-modifying therapeutics. In this review, converging clinical evidence defining lipid dyshomeostasis in early stages of AD is summarized followed by discussions on mechanisms by which lipid metabolism contributes to pathogenesis and modifies disease risk. Furthermore, existing and potential lipid-targeting therapeutic strategies are reviewed.

The accumulation of un- or misfolded proteins can lead to the formation of amorphous or ordered aggregates. Protein aggregation is often associated with human diseases and unravelling its underlying mechanism is critical for the development of diagnostic methods or treatments. However, investigating protein aggregation is challenging due to its complex and dynamic nature. Here, we summarized some popular methods to study the various aspects and steps involved in protein aggregation.

Ferroptosis is regulated by two transcription factors, NRF2 and BACH1, as its suppressor and promoter respectively. Here, we reviewed how these factors regulate execution of ferroptosis by changing ferroptosis-related metabolites (labile iron, glutathione and ubiquinol), lipid metabolism and cell differentiation. Ferroptosis is elaborately regulated by the competition of NRF2 and BACH1. Death signal is secreted from ferroptotic cells to surrounding cells, and its nature is also discussed.