Abnormal lipid remodeling of a lysosomal storage disease
Data files
May 20, 2026 version files 252.50 KB
Abstract
Lysosomes are integral organelles that communicate cellular status to an entire tissue through mechanisms that are poorly defined. We developed an unbiased platform, integrating human plasma metabolomes and single lysosome metabolomics, and show that the by-products of proteolysis are an unexpected class of signaling molecules. We show that dimethylarginine is a lysosomal-derived metabolite and predictor of patient morbidity. Genetic depletion of a lysosomal exporter, cystinosin, resulted in the accumulation of dimethylarginine in lysosomes. Leveraging a lysosomal storage disease with cystinosin mutations, we show that the rapid plasticity of dimethylarginine compartmentalization ensures cell and tissue homeostasis. Strikingly, lysosomal entrapment of dimethylarginine in patients and disease models corresponds with lipid accumulation, lipid droplets, and lipotoxicity. Exogenously restoring asymmetric dimethylarginine buffers oxidative stress, decreasing lipid peroxidation and cell death. These data show dimethylarginine engages an inter-organellar process–with peroxisomes, lysosomes, and lipid droplets–that confers a crucial adaptive response mechanism.
Dataset DOI: 10.5061/dryad.8931zcs5j
Description of the data and file structure
Untargeted lipidomic profiling of wildtype and CTNSKO HK2 cells.
This dataset contains the raw and normalized values of LC-MS untargeted lipidomics in wildtype and CTNSKOcells generated and analyzed with LipidSearch software (v4.2.21; www.thermofisher.com). Only peaks with molecular identification grade A or B were accepted (A: lipid class and FA completely identified; or B: lipid class and some FA identified).
Files and variables
Two Excel sheets are provided.
The first Excel sheet is titled "Untargeted_lipidomics_profiling_of_wildtype_and_CTNSKO_HK2_cells_(Raw)_.xlsx". There are two tabs in this Excel sheet. The first tab contains the unnormalized peaks of lipid species across the four conditions.
The second tab contains information regarding internal standards.
The second Excel is titled "Untargeted_lipidomics_profiling_of_wildtype_and_CTNSKO_HK2_cells_(Normalized).xlsx" and contains the normalized lipid species.
The data is displayed as nmol normalized to the internal standard and protein concentration.
A description of each column is as follows:
- Column A: Lipid Species
- Column B: Lipid Headgroup
- Column C: Chemical formula for lipid species
- Column D: Base retention rate for lipid species
- Columns E-G represent biological replicates of the wild-type HK2 cells treated with vehicle control for 24 hours.
- Columns H-J represent biological replicates of wild-type HK2 cells treated with 1mM ADMA for 24 hours.
- Columns K-M represent biological replicates of CTNSKO HK2 cells treated with vehicle control for 24 hours.
- Columns N-P represent biological replicates of CTNSKO HK2 cells treated with 1mM ADMA for 24 hours.
Code/software
No software is needed to view the data. No codes or scripts are needed. Any program that will open a spreadsheet, such as Microsoft Excel, is recommended.