Felix Kraus, Yuchen He, Sharan Swarup, Katherine A Overmyer, Yizhi Jiang, Johann Brenner, Cristina Capitanio, Anna Bieber, Annie Jen, Nicole M Nightingale, Benton J Anderson, Chan Lee, Joao A Paulo, Ian R Smith, Jürgen M Plitzko, Brenda A Schulman, Florian Wilfling, Joshua J Coon, J Wade Harper
Lysosomal storage diseases (LSDs) comprised ∼50 monogenic diseases characterized by the accumulation of cellular material in lysosomes and associated defects in lysosomal function, but systematic molecular phenotyping is lacking. Here, we develop a nanoflow-based multi-omic single-shot technology (nMOST) workflow allowing simultaneously quantify HeLa cell proteomes and lipidomes from more than two dozen LSD mutants, revealing diverse molecular phenotypes. Defects in delivery of ferritin and its autophagic receptor NCOA4 to lysosomes (ferritinophagy) were pronounced in NPC2 -/- cells, which correlated with increased lyso-phosphatidylcholine species and multi-lamellar membrane structures visualized by cryo-electron-tomography...
March 27, 2024: bioRxiv