Lysosomal proteome and lipidome analyses of intestinal cells reveal the crucial role of bis(monoacylglycero)phosphate for autophagosome-lysosome fusion
Del Gallo, G.; Chen, Z.; Sanner, A.; Hardt, R.; Merciai, F.; Salsano, F.; Bose, S.; Schweizer, M.; Medina, D. L.; Bosse, J. B.; Sommella, E. M.; Winter, D.; Jabs, S.; Braulke, T.
Show abstract
The transport of about 70 enzymes to lysosomes depends on mannose 6-phosphate signals formed by GNPTAB. Editing of Gnptab in an intestinal mouse cell line revealed the loss of multiple lysosomal enzymes associated with the accumulation of sphingomyelins, ceramides, and cholesterol, and reduced levels of bis(monoacylglycero)phosphate (BMP) in lysosomal proteomes and lipidomes. By cross-correlation we identified two subsets of lysosomal lipid-modifying enzymes linked with mixed unsaturated or di-monosaturated BMP. Autophagy-related proteins functioning in early stages of autophagosome formation associated with neutral ceramides, whereas proteins involved in autophagosome-lysosome fusion correlated with negatively charged BMPs. Therefore, the high cholesterol and low BMP level of lysosomes might be causal for impaired autophagic flux in GNPTAB deficient cells. We propose a functional axis of three lysosomal proteins as potential target to improve the autophagic flux in cells with dysfunctional lysosomes and in a newly established intestinal organoid model suitable as novel experimental tool.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- LC3 subfamily in cardiolipin-mediated mitophagy: A comparison of the LC3A, LC3B and LC3C homologs 92%
- Outer membrane vesicles produced by pathogenic strains of Escherichia coli block autophagic flux and exacerbate inflammasome activation 91%
- DYNC1LI2 regulates localization of the chaperone-mediated autophagy-receptor LAMP2A and improves cellular homeostasis in cystinosis 90%
Similar papers in this journal
- Fatty acid synthesis supports tumor progression through keeping TORC1 receptive for Insulin/PI3K signaling 91%
- Helicobacter pylori-induced adrenomedullin modulates IFN-γ-producing T-cell responses and contribute to gastritis 91%
- HOOK2 downregulation compromises the tumorigenic and stemness properties of ovarian cancer cells by increasing endoplasmic reticulum stress 87%
Similar papers in this journal
- TRPML1 activation ameliorates lysosomal phenotypes in CLN3 deficient retinal pigment epithelial cells 92%
- Lipid perturbation compromises UPR-mediated ER homeostasis as a result of premature degradation of membrane proteins 92%
- Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type-2 diabetes 92%
Similar papers in this journal
- Vagus nerve mediated liver-brain axis is a major regulator of the metabolic landscape in the liver 92%
- Perturbation of transmembrane 6 superfamily member 2 expression alters lipid metabolism in a human liver cell line 91%
- Ubiquitination is a novel post-translational modification of VMP1 in autophagy of human tumor cells 91%
Similar papers in this journal
- Basal Gp78-dependent mitophagy promotes mitochondrial health and limits mitochondrial ROS production 90%
- Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14 90%
- The Gb3-enriched CD59/flotillin plasma membrane domain regulates host cell invasion by Pseudomonas aeruginosa 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.