bims-proreb 2026-02-08 papers

Issue of 2026–02–08
four papers selected by
Shayan Motiei, Universität des Saarlandes

FEBS J. 2026 Jan 30.

Molecular chaperones and proteostasis regulation during cytosolic translation.

Molecular chaperones ensure that proteins attain their mature state by assisting in proper folding, preventing aggregation, refolding misfolded proteins, and targeting irreparably misfolded proteins for degradation. This comprehensive role is vital for maintaining cellular homeostasis and responding to stress conditions. In this review, I focus on the multifaceted roles of chaperones in regulating protein production, spanning from ribosome biogenesis to controlling translation rate and translation fidelity through the folding of essential translation factors in eukaryotes. I discuss the function of ribosome- and nascent chain-bound molecular chaperones for the translation machinery and protein synthesis. Finally, I highlight findings on the interdependence of the two pillars of protein homeostasis when cells experience cellular stress and organisms face pathophysiological conditions.

Keywords: chaperones; folding; proteostasis; ribosome biogenesis; translation

DOI: https://doi.org/10.1111/febs.70419

FEBS J. 2026 Feb 04.

Proteostasis of organelles in aging and disease.

Yara Nabawi, Cansu Doğan, Dunja Petrović, Gülce Perçin, Seda Koyuncu, David Vilchez.

To maintain proteome integrity within distinct subcellular compartments, cells rely on tightly regulated proteostasis mechanisms, including protein synthesis, folding, trafficking, and degradation. Disruption of these processes leads to the accumulation of damaged proteins and structural changes that progressively compromise organelle function, contributing to aging and age-associated disorders, such as neurodegeneration, cancer, and metabolic dysfunction. Here, we discuss recent insights into how proteostasis influences the integrity and function of specific organelles, including the nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes, as well as membraneless organelles, such as stress granules, processing bodies, the nucleolus, and nuclear speckles. We further discuss how dysfunction in these systems contributes to different hallmarks of aging and disease progression, highlighting potential therapeutic strategies aimed at maintaining organelle homeostasis to promote healthy aging.

Keywords: aging; cellular stress responses; membraneless organelles; membrane‐bound organelles; neurodegenerative diseases; organelle dysfunction; protein aggregation; proteostasis; stress granules

DOI: https://doi.org/10.1111/febs.70439

Cell Stress Chaperones. 2026 Jan 31. pii: S1355-8145(26)00003-9. [Epub ahead of print] 100147

The 13th International Symposium on Heat Shock Proteins in Biology, Medicine and the Environment: Honoring Legacy, Celebrating Scientific Advances, and Fostering Collaboration.

Laura J Blair, Richard Carpenter.

The 13th International Symposium on Heat Shock Proteins in Biology, Medicine and the Environment, organized by the Cell Stress Society International (CSSI), was held in October 2025 in Syracuse, NY, and brought together investigators spanning basic,translational, and clinical stress biology. The meeting highlighted the continued evolution of the heat shock response from a canonical transcriptional program to a complex, multi-layered network integrating transcriptional condensates, posttranslational regulation of chaperones, spatial organization, and system-level stress adaptation. Scientific sessions showcased advances in stress-induced transcription and genome control, the expanding Hsp90/Hsp70 "chaperone code," proteostasis and protein quality control, mitochondrial chaperones and metabolic regulation, cancer-immune interfaces, host-pathogen interactions, and the roles of chaperones in aging and neurodegenerative disease. Particular emphasis was placed on emerging therapeutic and diagnostic strategies, including isoform-specific chaperone inhibitors, co-chaperone targeting, theranostic approaches, and clinical-stage candidates. Systems-level analyses of stress resilience, extracellular chaperone signaling, and organismal adaptation further underscored the breadth of stress biology across scales. The symposium also honored the legacy of Dr. Len Neckers, whose pioneering contributions to Hsp90 biology shaped the field, and recognized outstanding scientific achievements through CSSI awards and fellowships. Collectively, the work presented reflects a field that continues to deepen mechanistic understanding while advancing toward precision-based therapeutic and diagnostic applications. This meeting report summarizes these developments and highlights future directions for stress biology research.

Keywords: heat shock response; molecular chaperones; proteostasis; stress-induced transcription

DOI: https://doi.org/10.1016/j.cstres.2026.100147

Biochem Biophys Res Commun. 2026 Feb 04. pii: S0006-291X(26)00170-1. [Epub ahead of print]805 153406

Spatial organization of ER-derived protein aggregates in the nucleus requires the Hsp70-family member BiP.

Shoukang Du, Yuhan Wang, Ting Gang Chew.

Cells maintain proteostasis by sequestering misfolded proteins into deposition sites. Aggregation-prone endoplasmic reticulum (ER) proteins form membrane-bound nuclear compartments that are cleared during cell division, yet the mechanisms underlying their spatial organization remain unclear. Here, using transcriptomic and proteomic analyses, we identified the ER-localized Hsp70 chaperone BiP as a key player. Genetic depletion or chemical inhibition of BiP prevented nuclear aggregate formation, while manipulating BiP regulators perturbed the aggregate formation. BiP-driven aggregation precedes the inner nuclear membrane synthesis that encapsulated the aggregates. Under proteostatic stress, nuclear aggregates localized adjacent to ER-derived aggregates. Our findings demonstrate that BiP is essential for organizing ER-derived aggregates in the nucleus, which further regulate nuclear proteostasis through spatial interactions with nuclear aggregates.

Keywords: BiP; Endoplasmic reticulum; Nucleus; Protein aggregates; Proteostasis

DOI: https://doi.org/10.1016/j.bbrc.2026.153406