Issues

Li et al. report a novel Cas9-based spatiotemporal gene-editing approach in zebrafish. Given the limited germline transmission efficiency of knock-in alleles in zebrafish, this system, featuring germline-specific nCas9^ERT2 expression driven by piwil1 promoter together with ubiquitously expressed gRNAs, enables rapid and high-throughput genetic screening in vivo.

Zhuang et al. introduce land-ExM, a superresolution approach that simultaneously maps protein and lipid ultrastructure in cells with high contrast. This method visualizes 3D interactions between membrane-bound organelles and phase-separated condensates, uncovering organelle contact sites such as stress granules at nuclear tunnels adjacent to nucleoli.

Prado-Mantilla et al. develop a mouse line to allow cell type–specific, rapid, and reversible degradation of GFP-tagged proteins. Using this line, they demonstrate distinct functional roles for the glucocorticoid receptor in proliferative and differentiated cells of the epidermis.

Falk et al. identify a mechanism coupling mitochondrial movement to energy demand. When energy levels are low, the energy-sensing kinase AMPK phosphorylates the motor/adaptor protein TRAK1, arresting mitochondria via the actin cytoskeleton. This mechanism likely helps to position mitochondria where they are most needed.

Luan et al. identify the cullin-3 adaptor SHKBP1 as a noncanonical regulator of p62 phase behavior that limits p62 body formation, restrains Keap1 sequestration, and tunes Nrf2-dependent antioxidant responses to oxidative stress.

DMIM (also called MTSS1) promotes Rac1-mediated branched actin network formation and endocytosis to drive rapid, cyclical plasma membrane remodeling during embryonic syncytial divisions. Loss of DMIM leads to decreased branched actin networks and a coincident increase in bundled actin networks induced by RhoGEF2 and diaphanous.

Liu et al. report that linker extension in ESCRT-III converts flat spirals into rings, abolishing their capacity to execute membrane abscission for intraluminal vesicle formation. These findings establish the linker as a key regulator of assembly and confirm the essential role of the flat spiral conformation.

The decline of mitochondrial function with age is observed widely among organisms. In a screen to identify mutants that delay this decline, Waite et al. discover that potassium, the most abundant cation in cells, modulates mitochondrial membrane potential—a functional hallmark of mitochondrial health. This study links together mitochondrial health, potassium homeostasis, and cellular aging.

Hundreds of proteins are targeted to mitochondria via presequences. Multiple proteins have been postulated to harbor “weak” or “strong” presequences, but how these strengths are defined remains unclear. Here, Yan et al. define quantitative parameters underlying presequence strength and demonstrate that yeast require strong presequences to facilitate select metabolic pathways in mitochondria.

Ambrosio et al. discover GRIPAP1 is a component of the cellular machinery that produces the platelet α-granule, a member of the lysosome-related organelle family. GRIPAP1 is an elongated homodimer functioning as a tethering factor at recycling endosome subdomains that mediate traffic of both biosynthetic and endocytosed proteins to the α-granule.

Schematics typically depict the actomyosin cortex below flat PM, but cells have complex PM topographies. Over the early Drosophila embryo, a composite of actomyosin and PM folds conveys cortical tension, and regulation involves PM topography modulation by Arp2/3.

Zych et al. demonstrate that reduced RCC1 levels in micronuclei impair protein export, causing persistent micronuclear growth, nuclear lamina gap expansion, and rupture. In small micronuclei, chromatin state–dependent RCC1 depletion further disrupts nuclear import, inhibiting growth and micronucleus rupture.

Chromosome territories are a hallmark of interphase nuclear organization, yet the underlying mechanisms remain unclear. This study shows that condensin II collaborates with cohesin to establish and maintain chromosome territories, revealing a cooperative mechanism supporting large-scale genome organization in interphase.

The amounts of sphingomyelin and cholesterol in organelle membranes are coordinately regulated. Depletion of cholesterol increases sphingomyelin synthesis resulting from increased coatomer II–mediated endoplasmic reticulum-to-Golgi trafficking of ceramide, the precursor to sphingomyelin. The coatomer II network protein cTAGE5 is proposed to sort ceramide-rich membrane into endoplasmic reticulum cargo exit sites.

Hamrick and Rog define the organization of the sister chromatids during meiosis in the nematode Caenorhabditis elegans. Meiotic exchanges are formed in the context of four DNA molecules: two identical sisters, each from the two parental chromosomes. Here, the sisters are found to occupy distinct volumes when exchanges form.