Volume 25 Issue 11, November 2023

Reliable ways to identify senescent cells represent a bottleneck for understanding the roles of senescence in physiology and disease. This Comment examines the challenges of identifying senescent cells, revises existing recommendations for how to best assess senescence and discusses how emerging technologies can address these issues.

Conferences are often held at different venues and feature innovative scientific programs; however, their design rarely changes, and barriers that exclude marginalized scientists persist. We discuss why this is a problem and offer suggestions for people and organizations seeking to create more inclusive and sustainable scientific meetings.

The bacterial pathogen Legionella pneumophila uses effectors — toxins — to facilitate pathogenesis within host cells. A recent study identifies dual mechanisms of the effector SidI as an inhibitor of translation elongation. The N-terminal domain mimics tRNA, whereas the C-terminal domain glycosylates the ribosome.

Cells use diverse mechanisms to rid themselves of dysfunctional or excess mitochondria. A study now shows that C. elegans sperm use a previously undescribed mechanism to rapidly expel single healthy mitochondria in membrane-bound structures called mitophers.

How spatial organization in the cell is achieved on the organelle scale is unclear. A new study finds that tethering specific proteins near the surface of micelle-like paraspeckles modifies their properties and determines whether these subnuclear organelles are separate from, adhere to, or are engulfed by nuclear speckles.

Disruption of ribosome assembly results in the accumulation of aggregation-prone ‘orphaned’ ribosomal proteins that are toxic to cells if left unchecked. A study finds that cells store such ribosomal proteins during heat shock to enable a quick recovery of ribosome assembly after the removal of this stress.

YTHDF family members are ‘readers’ of a common mRNA modification, but their effects on mRNA translation and stability have been disputed. A new study shows that YTHDF1 and YTHDF3 are post-translationally regulated through O-GlcNAcylation, unifying disparate results and pointing to environmental cues that could modulate YTHDF function.

The fibrous geometry of extracellular matrices (ECMs) is believed to facilitate cell adhesion, but a mechanistic link is lacking. We uncover a type of integrin-mediated cell adhesion — ‘curved adhesion’ — driven by the fibrous geometry of the ECM. Curved adhesions are induced by membrane curvature, enabling cell adhesion to soft three-dimensional (3D) ECM fibres.

Kramer, Prakash et al. share genome-wide CRISPR screens for factors that alter the levels of two dual-genome-encoded Complex IV subunits, COX1 and COX4. They identify PREPL and NME6 as genes that connect mitochondrial metabolism to mtDNA expression.

Sanfeliu-Cerdán et al. show that an SH3-domain-induced rigidity transition of MEC-2/stomatin condensates enables mechanotranduction of external forces in C. elegans touch receptor neurons.

Subramanian et al. show that the secreted Legionella protein SidI is a tRNA mimic and glycosyltransferase. SidI inhibits host cell translation by mannosylating ribosomes to induce ribosome collisions and trigger the ribotoxic stress response.

Tai et al. show that Hem25p—a mitochondrial glycine transporter required for haem biosynthesis—is also needed for isopentenyl pyrophosphate (IPP) transport into mitochondria and coenzyme Q synthesis in Saccharomyces cerevisiae.

Liu et al. describe mitopherogenesis: the secretion of mitochondria in mitophers during sperm development in Caenorhabditis elegans, which is important to control the mitochondrial pool and ensure fertility.

Sha et al. show that Borealin is a non-canonical methylation substrate for MLL1 that regulates phase separation of the inner centromeric chromosome passenger complex, and dictates genome integrity and tumour development in hepatocellular carcinoma.

Wang et al. report that the secretory coat protein complex COPII undergoes liquid–liquid phase separation that is tuned by manganese in the cytosol, to impact lipoprotein secretion.

Takakuwa, Yamazaki et al. show that the long noncoding RNA NEAT1 domains specify a set of proteins that localize to the outer shell and distinguish nuclear speckles from paraspeckles to preserve their structural identity.

Chen et al. report that the YTHDF family of m⁶A-RNA-binding proteins can be differentially regulated by the post-translational modification O-GlcNAcylation, leading to differential regulation of the YTHDF proteins on translation and phase separation.

Ali et al. show that, during heat shock, aggregation-prone orphan ribosomal proteins form nucleolar-associated condensates that are kept in a liquid-like and reusable state through Hsp70 and its co-chaperones.

Through a CRISPR-activation screen, Ravid Lustig et al. show that GATA transcription factors activate long-range Xist enhancers to upregulate Xist expression and initiate X chromosome inactivation in early mouse embryos.