Proteomic and phosphoproteomic analyses of lysosomes identify a nutrient-independent regulatory arm of mTORC1 signalling that mediates lysosomal adaptation to stress and whose deregulation underl...

Lennartz et al. evaluate lipid enrichment in clathrin-coated pits and observe that the differential lipid partitioning into clathrin-coated pits is largely driven by the lipid asymmetry of the plasma ...

The autophagy core machinery mediates the enclosure of cytosolic cargo destined for degradation in the lysosome. The Atg9-Atg2-Atg18 complex coordinates phagophore expansion via directed lipid transfe...

Proteoforms are the diverse protein molecules produced from a single gene whose primary sequence and composition can be diversified by genetic, transcriptomic, translational and post-translational var...

The sequential assembly of over 50 proteins during clathrin-mediated endocytosis (CME) is well documented in yeast. However, the mechanisms governing this ordered recruitment remain poorly understood....

IRIS learns conserved signaling representations from in vitro perturbation data to reconstruct signaling states and histories across diverse in vivo cellular contexts.

Yatskevich et al. show that HUWE1 amplifies existing ubiquitin tags through chain elongation and branching. A cryo-EM structure reveals multivalent HUWE1-USP7 assembly and reciprocal regulation, while HAPSTR1 tunes substrate capture by engaging HUWE1 ubiquitin-binding motifs, defining a coordinated system for short-lived nuclear protein turnover.

Damaged mitochondria are cleared by lysosomes. Here, authors show that ER-to-lysosome cholesterol transport preserves lysosomal degradative function during mitophagy, enabling efficient recycling of l...

Radulovic et al. show that phosphatidylinositol 3-phosphate (PI3P), produced by the phosphatidylinositol 3-kinase PIK3C3, is formed on ER domains after lysosome damage. ER domain PI3P helps to recruit...

Two studies show that the endoplasmic reticulum-associated protein CLN8 catalyses the acyl CoA-dependent acylation of glycerophosphoglycerol, producing lysophosphatidylglycerol, which is then converte...

Agarwal et al. introduce MitoSpace, a self-supervised model trained on 4D lattice light-sheet microscopy data. The model resolves drug-induced mitochondrial phenotypes without labels, predicts membran...

Yang et al. reveal that the ARLA1A-NAC089 module couples ER phagy with the UPR in plants. This dual regulatory axis fine-tunes cell survival versus death under stress, providing a mechanistic framework for maintaining ER homeostasis and enhancing environmental resilience.

MemBrain v2 enables streamlined analysis of membranes in cryo-electron tomography by providing user-friendly tools for membrane segmentation, membrane protein localization and spatial analysis, suppor...

Labeling the plasma membrane for advanced imaging remains a significant challenge. For time-lapse live cell imaging, probe internalization and photobleaching are major limitations affecting most membr...

The mitochondrial inner membrane complexes TIM23 and TIM22 mediate distinct protein topogenesis functions in polypeptide import. The authors reveal their mechanistic overlap in topogenic sequence reco...

Mitochondrial cristae are essential for respiration, yet the molecular basis of how the high curvature of these membrane folds is maintained remains unclear. Using structure prediction tools and multi...

Protein-protein interactions (PPIs) mediate diverse cellular processes, but PPIs are typically characterized using reconstituted in vitro biochemical and biophysical approaches. Current approaches for...

Inefficient endosomal escape is a crucial barrier to intracellular delivery of nucleic acid therapeutics using lipid nanoparticles (LNPs). The use of ionizable lipids (ILs) has significantly improved ...

TMEM165 is a Golgi-resident multi-pass membrane protein involved in divalent cation homeostasis and associated with congenital disorders of glycosylation, yet its N-terminal biogenesis has remained un...

Li et al. identify TMEM141 as a negative regulator of mitochondrial complex I assembly. Under high energy demand, the YME1L1 and AFG3L2 proteases degrade TMEM141, relieving its inhibition of the assembly factor TIMMDC1. This work reveals a mechanism that adapts complex I assembly to OXPHOS demands.

Nature Reviews Clinical Oncology, Published online: 19 August 2026; doi:10.1038/s41571-026-01190-7Despite considerable progress in other cancer types, progress with the development of targeted therapies for patients with glioblastoma has remained limited, despite considerable research effort. In this Review, the authors summarize the various attempts to develop effective targeted therapies for patients with glioblastoma, including some of the challenges that have likely impaired progress thus far. The authors also highlight novel therapies, clinical trial designs and research directions that have been informed by the shortcomings of previous research efforts, all of which might eventually lead to improved outcomes for patients.

Tau protein aggregates adopt distinct conformations across tauopathies, yet the protein interactions engaged by disease-specific polymorphs remain poorly characterized. Here, we demonstrate that confo...

The Human ULK1 autophagy-initiating complex consists of ULK1, FIP200, and the HORMA domain heterodimer ATG13:ATG101. PI3P is essential to recruit ULK1C to membranes for ULK1, but ULK1C subunits do not...

Proteomic and transcriptomic profiling on hiPSC-derived midbrain dopaminergic neurons with pathological α-synuclein burden reveals defective Sec61A interactions and co-translational translocation of E...