- VDAC2–BAK axis permeabilizes peroxisome membrane
VDAC2 controls the stable localization of BAK to mitochondria and its ability to mediate mitochondrial outer membrane permeabilization. Hosoi et al. now report that BAK shifts from mitochondria to peroxisomes under VDAC2-deficient conditions, giving rise to the mislocalization of peroxisomal matrix proteins such as catalase, which suggests that BAK can also regulate the permeability of peroxisomal membranes.
- MPC activity regulates excitotoxicity
In cortical neurons and hippocampal slice cultures, blocking mitochondrial pyruvate uptake rewires metabolism to increase reliance on glutamate to fuel the TCA cycle. This diminishes the readily releasable pool of neuronal glutamate and minimizes the positive-feedback cascade of excitotoxic injury.
- Telomeres as therapeutic targets
Martínez and Blasco review the molecular mechanisms underlying diseases associated with telomere dysfunction, including telomeropathies, age-related disorders, and cancer. Current and future therapeutic strategies to treat and prevent these diseases, including preclinical development of telomere-targeted therapies using mouse models, are discussed.
- Membrane bending by Mic60 is conserved
The multisubunit mitochondrial contact site and cristae organizing system (MICOS) plays an important role in cristae junction formation. Tarasenko et al. show that the MICOS component Mic60 actively bends membranes and that this activity is evolutionarily conserved and necessary for cristae structure.
- KDM3A regulation of actin affects IFT
Yeyati et al. demonstrate that the histone demethylase KDM3A acts as a negative regulator of ciliogenesis by modulating actin dynamics, both transcriptionally and by directly binding actin. KDM3A influences local actin networks to restrict intraflagellar transport during ciliogenesis; in its absence, cilia become unstable with abnormal lengths and accumulated intraflagellar transport proteins.
- DGCR8 is required to exit pluripotency
DGCR8 is essential for mouse early development and microRNA biogenesis. Cirera-Salinas et al. report a new noncanonical function of DGCR8 essential for the exit from pluripotency of mouse embryonic stem cells.
- Structure and lipid binding of the Vps13–Cdc31p complex
VPS13 proteins are widely conserved in eukaryotes and associated with human neurodegenerative and neurodevelopmental diseases. De et al. describe the lipid specificity and structure of yeast Vps13p, providing insight into its role in both TGN late endosome transport and TGN homotypic fusion.
- Molecular basis of receptor-mediated transcytosis
Transcytosis plays an important role in establishing cell polarity and in mediating transport of large cargo across epithelial barriers, but its molecular basis is unclear. Nelms et al. present a new dataset of genes involved in receptor-mediated transcytosis and show that the apical and basolateral recycling and transcytotic pathways are genetically separable.
- FKB-6 in meiotic chromosome pairing and synapsis
Dynein-mediated movement of microtubules is required for chromosome movement; its absence leads to aberrant segregation. Alleva et al. show that FKB-6, a cochaperone of Hsp-90, is required for proper chromosome movement through down-regulation of resting time between movements.
- A new family of eukaryotic kinetochore proteins
The kinetochore complex is conserved across many eukaryotes, but the protozoan lineage Kinetoplastida builds kinetochores from components without apparent homology to models. D’Archivio and Wickstead describe a new family of proteins with homology to outer kinetochore proteins Ndc80 and Nuf2 that defines the outer kinetochore of trypanosomes, suggesting that all eukaryotes have divergent versions of a universal kinetochore machine.