Here the author highlights and summarizes the latest advances in ribosome-associated quality control and related mechanisms.

In this review, the authors discuss and contextualize the cellular responses launched after mitochondrial stress and note the importance of the emerging understanding in applying this new knowledge in relevant diseases.

In this Review, Kotani and Nakatogawa discuss recent advances in our understanding of the molecular basis of autophagy induction and delineate how diverse mechanisms converge on core principles to ensure context-specific control of autophagy initiation.

Protein homeostasis is essential for cell health and function, with the proteostasis network safeguarding protein production, folding and degradation. Disruption of any of the multiple pathways involved is a hallmark of aging and many pathologies. We asked experts studying proteostasis to share with us which unresolved questions they are most interested in addressing and how they envision the field in the future.

Burr and Auckland et. al develop MitoPerturb-Seq, which combines single-cell screening with multiomics to link nuclear genes to mitochondrial DNA (mtDNA) dynamics. They unveil core regulators of mtDNA copy number and characterize cell-cycle delays and transcriptional stress in response to mtDNA depletion.

Dutta et al. demonstrate that the tumor suppressor complex BRCA1–BARD1 physically interacts with the RNA–DNA helicase Senataxin (SETX) and upregulates the activity of SETX to resolve harmful R-loops crucial for the avoidance of transcription–replication conflicts.

Liu et al. show that the C9orf72 GGGGCC-repeat RNA drives liquid-to-solid phase transition of poly(GR) in ALS/FTD through forming G-quadruplex and hairpin scaffolds, whereas targeting the RNA structures with small molecules reduces poly(GR) aggregation and cellular dysfunction.

Wang, Guo, Zhang and colleagues obtain four cryo-electron microscopy snapshots that show how IscB is kept off by two RNA lids, with a car-pedal-like guide shift activating cleavage after ~11-nt pairing. They also engineer hinge regions that boost flexibility and improve genome editing in cells.

Zheng et al. show that extending the guide RNA restores the reduced activity of a high-fidelity CRISPR–Cas9 enzyme while preserving accuracy, revealing how strengthened PAM-distal interactions can improve genome-editing performance.

Here, Deol et al. use genetic screens in gene-edited reporter cell lines to identify regulators of ferroptosis suppressor protein 1 (FSP1) expression and stability. They show that vitamin B2 metabolism stabilizes FSP1 through flavin adenine dinucleotide binding, preventing its degradation and ferroptosis sensitization.

In this issue of Nature Structural & Molecular Biology, we focus on all things protein homeostasis, highlighting a variety of processes, from protein quality control in translation to autophagy.

The partnership between a leading European research institute, the European Molecular Biology Laboratory (EMBL), and a pharmaceutical company, GSK, has set an example of how to build a successful academia–industry relationship. Here, we reflect on the key success factors that shaped this partnership.

In this issue of Nature Structural & Molecular Biology, we are publishing two studies investigating the mechanisms of how bacteria fight phage invasion, and how phages fight back.