Lupus & antiphospholipid syndrome
Crotonylome profiling identifies MLKL crotonylation in lupus nephritis associated with RAB1A–mTOR signalling and autophagy changes in tubular epithelial cells
Authors' conclusion
MLKL crotonylation is associated with activation of the RAB1A-mTOR axis and altered tubular autophagy-lysosome pathway homeostasis in LN.
Study context
- Population
- Patients with lupus nephritis (LN), patients with SLE without nephritis and healthy controls (PBMCs, renal biopsy tissues); LPS-stimulated HK-2 cells
- Comparison
- LN vs SLE without nephritis vs healthy controls
Methodological detailscrotonylome proteomics, renal biopsy tissue analysis, in vitro HK-2 cell experiments, siRNA-mediated knockdown
- Crotonylome proteomics
- Renal biopsy tissue analysis
- In vitro HK-2 cell experiments
- siRNA-mediated knockdown
Main finding
As reported in the abstract
- MLKL identified as a differentially crotonylated protein in LN, with increased crotonylation at K95 and K219
- LN kidney tissue: increased fibronectin and collagen III deposition vs controls; no significant difference between class IV and class V LN
- LC3 signal did not differ significantly between groups; LAMP1 expression and LC3-LAMP1 co-localisation reduced in LN
- HK-2 cells: crotonylation-deficient MLKL mutants associated with increased LC3-II and reduced p62; K219Q showed the opposite pattern
- BafA1 flux assays: K219R cells had higher LC3-II than WT before and after lysosomal inhibition, with comparable BafA1-induced LC3-II accumulation, consistent with increased autophagosome formation rather than impaired lysosomal degradation
- HDAC1 knockdown increased MLKL crotonylation, accompanied by mTOR activation
- MLKL crotonylation enhanced RAB1A GTP binding without altering total RAB1A abundance
- RAB1A knockdown in MLKL WT cells attenuated mTOR phosphorylation and partly reversed the autophagy-suppressive marker profile
- Sodium crotonate induced an autophagy-suppressive marker profile partly reversed by rapamycin
Original publication
Crotonylome profiling identifies MLKL crotonylation in lupus nephritis associated with RAB1A–mTOR signalling and autophagy changes in tubular epithelial cells. Lupus Sci Med. Published 31 August 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →