Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST.

ABSTRACT: Lysosomal storage diseases (LSDs) comprise ~50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multi-omic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially in NPC1 ^-/- and NPC2 ^-/- mutants, where lysosomes accumulate cholesterol. Autophagic and endocytic cargo delivery failures correlated with elevated lyso-phosphatidylcholine species and multi-lamellar structures visualized by cr

SUBMITTER: Kraus F 

PROVIDER: S-EPMC10996675 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature