Lipid-induced granules in hepatocytes alleviate liver fibrosis
In addition to already known intracellular membraneless organelles, like granules, bodies, speckles, etc., recently researchers discovered a new membraneless organelles.
DEAD-box helicase (DDX) family members possess the potential to undergo liquid-liquid phase separation (LLPS), the foundation for the assembly of membraneless organelles.
The researchers in this study identify new granules with arachidonic acid (AA) metabolites induced LLPS of DDX49 in hepatocytes, forming an assembled granule named as lipid-induced granule (LIG).
The researchers show that C5-methylcytosine (m5C)-modified mRNA of pro-fibrotic hepatokine tissue inhibitor of metalloproteinase 2 (Timp2) and its reader Y-box binding protein 1 (YBX1) were recruited into LIGs, thereby inhibiting Timp2 mRNA translation and consequently feedback suppressing liver fibrosis.
The authors also identified LIGs were in human MASLD livers and exhibited reverse correlation with fibrosis progression.
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(25)00546-7
