01
Yifan Dai, et al.
Cell. 2024.
This study investigates the role of biomolecular condensates in modulating the cytoplasmic ion environment and their effects on cellular electrochemical equilibria. Biomolecular condensates are micro-scale structures formed through the phase transition of multivalent biomacromolecules. The research explores how these condensates can spatially segregate ions, creating pH gradients and electric potential differences between the dilute and dense phases. Using simulations and experimental data, the study demonstrates that condensate formation by intrinsically disordered proteins, like resilin-like polypeptides (RLPs), generates electrical potential gradients that can drive redox reactions. The findings reveal that these ion gradients and potential differences impact the cytoplasmic ionic environment, influencing cellular membrane potentials and overall cellular functions. The research also highlights how the volume fraction of condensates affects gene expression and cellular interactions, showing that condensates contribute to cellular heterogeneity by regulating electrochemical equilibria. This study uncovers a novel functional role for biomolecular condensates in global cellular processes, providing insights into how they modulate cellular physiology beyond their established roles in protein concentration homeostasis.
DOI: 10.1016/j.cell.2024.08.018
02
Pietro Fontana, et al.
Cell. 2024.
This study explores the potential of activating gasdermin D (GSDMD) to enhance antitumor immunity. Gasdermins, particularly GSDMD, are involved in pyroptosis, an immunogenic form of cell death that could boost immune responses against cancer cells. The research focuses on a small molecule, DMB, which activates GSDMD without requiring cleavage. This activation induces pyroptotic death in tumor cells, leading to the release of damage-associated molecules that stimulate immune responses. Using DMB, the study demonstrated increased antitumor immunity in several mouse tumor models and found that GSDMD expression in tumor cells is crucial for this effect. Additionally, DMB treatment enhanced the efficacy of anti-PD-1 therapy in a model resistant to either treatment alone. The study highlights that small-molecule activation of GSDMD can effectively trigger antitumor immunity while minimizing systemic toxicity, suggesting a promising approach for treating cancers with positive GSDMD expression.
DOI: 10.1016/j.cell.2024.08.007
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