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β-propeller protein-associated neurodegeneration (BPAN) is caused by loss of functional WIPI4. A new study reports that depletion of WIPI4 induces ferroptosis via changes in mitochondrial membrane lipids, independently of the role of WIPI4 in autophagy, providing insights into the cause of neurodegeneration in BPAN.
Zhu et al. show that loss of WIPI4, as seen in β-propeller protein-associated neurodegeneration, causes ferroptosis independently of autophagy due to an imbalance in phosphatidylethanolamine levels.
Mathiowetz and Olzmann review our current understanding of the mechanisms of lipid droplet biogenesis and turnover, the transfer of lipids and metabolites at membrane contact sites, and the role of lipid droplets in regulating fatty acid flux in lipotoxicity and cell death.
Weatherbee, Weberling, Gantner et al. find contrasting requirements for BMP in the anterior signalling centre and pre-implantation epiblast between mice and humans. They further find that NOTCH may be indispensable for human epiblast survival.
The tumour microenvironment produces nutrients that propel cancer development. New work finds that pancreatic ductal adenocarcinoma cells use one such nutrient, acetate, to alter protein acetylation, rerouting polyamine metabolism and promoting cell growth under acidosis—a finding with potential implications for treating this cancer.
The endoplasmic reticulum (ER) controls the synthesis of lipids and proteins and Ca2+ homeostasis, as well as contacting other organelles and the plasma membrane. A study now looks at a process by which this compartment is remodelled in axons during neurogenesis: the lysosomal clearance of ER subdomains, driven by FAM134 and CCPG1 proteins.
In this Perspective, Zhang discusses the latest advances in understanding of iron function, regulation and metabolism, as well as the implications for ferroptosis in health and disease.
Murthy et al. demonstrate that cancer-associated fibroblast-derived acetate regulates polyamine homeostasis via an ACSS2–SP1–SAT1 axis in pancreatic cancer cells, thus enabling cell survival and tumour development under acidosis.
Hoyer et al. establish that selective autophagy mechanisms are needed to remodel the ER and its proteome during in vitro neurogenesis across neuronal subcompartments and decode the substrate selectivity of ER-phagy receptors.
Biomolecular condensates are recognized for their ability to compartmentalize the cytoplasm without bounding membranes, but the degree to which they organize the cytoplasm has not been clear. A new study reveals that condensates at a scale of 100 nm are responsible for the organization of at least 18% of the cytoplasmic proteome.
Keber et al. use filtration chromatography and quantitative proteomics of Xenopus egg extracts and show that at least 18% of cytoplasmic proteins are organized in small ~100-nm biomolecular condensates.
Rai et al. report that CAMSAPs can bind to minus ends of microtubules attached to γ-tubulin ring complex (γ-TuRC) and drive microtubule release. They show that CDK5RAP2, but not CLASP2, inhibits CAMSAP-mediated microtubule release from γ-TuRC.
In this Review, Dai, Stockwell, Kroemer, Tang and colleagues offer a comprehensive discussion of the molecular regulation of ferroptosis and highlight how this may be potentially leveraged for therapeutic benefit for disease treatment.
Activation of innate immunity has been linked to the progression of type 1 diabetes. A study now shows that overexpression of METTL3, a writer protein of the m6A machinery that modifies mRNA, restrains interferon-stimulated genes when expressed in pancreatic β-cells, identifying it as a promising therapeutic target.
De Jesus et al. describe the redox-mediated regulation of m6A writer methyltransferase 3, which blunts innate immune responses by modification of RNA sensor and editor component mRNAs during the onset of type 1 diabetes in β-cells.
Scientists must actively advocate for infrastructure development and funding of emerging research directions through collective efforts. In India, this has been crucial to help reverse the brain drain and enable equitable contributions to research and development at the global level.