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Ferroptosis can be induced by lipid peroxidation in various subcellular membranes, including the endoplasmic reticulum (ER), mitochondria and lysosomes. By studying the subcellular distribution of ferroptosis-modulating fatty acids, we observed that the ER is a key initial site of peroxidation, followed by the plasma membrane, whereas other organelles are not as critical for ferroptosis.
Etoposide, a chemotherapeutic poison of type IIA eukaryotic topoisomerases (topo IIs), promotes topo II to compact DNA by trapping DNA loops, creates DNA double-strand breaks, causes topo II to resist relocation, and pauses the ability of topoisomerases to relax DNA supercoiling. Through these mechanisms, etoposide converts topo II into a roadblock to DNA processing.
GPCRs are selective for specific G-protein subtypes, thereby ensuring signaling fidelity. A new report finds that that empty-like G-protein mutants are promiscuously recognized by GPCRs, suggesting that receptors select cognate over non-cognate G proteins at steps preceding nucleotide release.
Modern drug discovery relies upon intelligent exploration of ‘in stock’ and ‘on demand’ virtual libraries of compounds. A comparative analysis highlights the explosive expansion of accessible chemical space and also reveals challenges and opportunities arising for computational drug discovery.
Analysis of cell–cell communication between embryonic stem cells using a combination of experiments and modeling shows that cells can communicate important messages over much larger distances than previously known, exhibiting quorum-sensing-like behavior.