Volume 27 Issue 2, February 2025

In each cell division during early embryogenesis, daughter cells acquire half the size of the mother cell. A study now reports that cytoplasmic flows sensing the cell boundaries allow daughter cells to adapt to their new size and reform their nuclear envelope in the right position.

The clearance of biomacromolecules through selective autophagy is crucial for cellular homeostasis. A study now identifies receptor mobility as a key factor influencing cargo degradability. A dynamic cargo–receptor surface enables phase separation of essential autophagy initiation proteins, which drives phagophore formation.

Nuclear speckles are dynamic structures enriched in RNA and RNA regulators, with varying compositions. A study now reports two distinct signatures of nuclear speckles that are linked to the prognosis of clear cell renal cell carcinoma. The signatures influence the expression of genes regulated by the transcription factor HIF2α.

Accurate protein targeting is a crucial aspect of many biological pathways such as ribosome assembly. Most eukaryotes require two sets of ribosomes assembled in the nucleus and mitochondria. A new study reveals how a cytoplasmic ribosomal protein uS5 evolved a unique signal to avoid being mistargeted to the mitochondria.

We devised a multiomics strategy to identify metabolic pathways used by yeast to surmount mitochondrial stress. Strains capable of recovery relied on triacylglycerol mobilization to provide acyl groups for nascent cardiolipin biosynthesis during mitochondrial biogenesis. We further linked multiple proteins to this mobilization phenotype, including essential lipases in both yeast and mammalian model systems.

Blocking the translocase of the outer membrane (TOM) channel induces elimination of unoccupied protein import channels in the inner membrane by an ATP-dependent protease. Precursor-dependent adjustment of the number of translocator channels provides new insights into mitochondrial quality control upon protein import stress.

Cells respond to mitochondrial protein import stress by regenerating clogged import sites and inducing stress responses. Mitochondria are thus tightly integrated into the cellular proteostasis and stress-response network to maintain cell viability.

Pashos et al. show that H3K36 methylation maintains intestinal epithelial fate commitment, whereas its suppression, which is also observed upon injury, induces a plastic state and expression of genes involved in regeneration.

Hemalatha et al. track the endogenous redox ratio (NAD(P)H/FAD) with live imaging in the mouse skin to study the interface of wild-type stem cells with oncogenic mutant cells. They find that maintaining a robust redox ratio is key to clonal prevalence.

Ma et al. show that heterogeneous nuclear ribonucleoprotein U promotes the primed state in human pluripotent stem cells by interacting with nuclear matrix protein, Matrin-3, and regulating primed-specific genes.

Wang et al. profile the translatome of haematopoietic stem cells (HSCs) and downstream progenitors and lineages. They identify the SNORD113–114 cluster as a modulator of translation and self-renewal in HSCs.

Fulcher et al. show that MDM2 times mitosis through self-catalysed ubiquitination and proteasomal destruction, triggering G1 arrest following delays in mitosis associated with chromosome instability and aneuploidy.

Afonso et al. show that, during anaphase, chromosome movement can be driven by large cytoplasmic flows. These dynein-dependent cytoplasmic flows scale with cell size, slowing in smaller cells, thereby scaling anaphase.

Licheva, Pflaum, Babic, Mancilla et al. show that low-affinity cargo–receptor interactions promote autophagy receptor mobility and condensation of the scaffold protein Atg11 to trigger initiation hub and phagophore formation.

Baker et al. show that mitochondrial stress recovery requires mobilization of lipid droplet triacylglycerol stores to facilitate cardiolipin biosynthesis and mitochondrial biogenesis.

Hsu et al. show that mitochondrial import blockage stress activates the ATP-dependent protease YME1L1, which degrades mitochondrial presequence translocase TIM23 subunits to promote cell growth.

This study reports that nuclear speckle constituents have two expression states in cancer correlating with patient survival and HIF-2α functional programs. HIF-2α mediates nuclear speckle association of key genes activated in renal cancer.

Oborská-Oplová et al. report a conserved mitochondrial avoidance segment in the cytosolic ribosomal protein uS5 that prevents mistargeting of uS5 to the mitochondrial matrix and ensures cytosolic ribosomal assembly.

Sojka et al. analyse the transcriptomic and epigenomic landscape of human astrocyte maturation and identify an epigenetically regulated intermediate state associated with aberrant development in glioblastoma.

Guo and colleagues characterize an intact Carnegie stage 7 human embryo at single-cell resolution in a spatially resolved manner.