Identification of TFG- and Autophagy-Regulated Proteins and Glycerophospholipids in B Cells.
J Proteome Res
; 23(5): 1615-1633, 2024 May 03.
Article
in En
| MEDLINE
| ID: mdl-38649144
ABSTRACT
Autophagy supervises the proteostasis and survival of B lymphocytic cells. Trk-fused gene (TFG) promotes autophagosome-lysosome flux in murine CH12 B cells, as well as their survival. Hence, quantitative proteomics of CH12tfgKO and WT B cells in combination with lysosomal inhibition should identify proteins that are prone to lysosomal degradation and contribute to autophagy and B cell survival. Lysosome inhibition via NH4Cl unexpectedly reduced a number of proteins but increased a large cluster of translational, ribosomal, and mitochondrial proteins, independent of TFG. Hence, we propose a role for lysosomes in ribophagy in B cells. TFG-regulated proteins include CD74, BCL10, or the immunoglobulin JCHAIN. Gene ontology (GO) analysis reveals that proteins regulated by TFG alone, or in concert with lysosomes, localize to mitochondria and membrane-bound organelles. Likewise, TFG regulates the abundance of metabolic enzymes, such as ALDOC and the fatty acid-activating enzyme ACOT9. To test consequently for a function of TFG in lipid metabolism, we performed shotgun lipidomics of glycerophospholipids. Total phosphatidylglycerol is more abundant in CH12tfgKO B cells. Several glycerophospholipid species with similar acyl side chains, such as 362 phosphatidylethanolamine and 362 phosphatidylinositol, show a dysequilibrium. We suggest a role for TFG in lipid homeostasis, mitochondrial functions, translation, and metabolism in B cells.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Autophagy
/
B-Lymphocytes
/
Glycerophospholipids
/
Lysosomes
Limits:
Animals
Language:
En
Journal:
J Proteome Res
Journal subject:
BIOQUIMICA
Year:
2024
Type:
Article
Affiliation country:
Germany