The physiological role of lipid asymmetry in intracellular membranes remains poorly understood. However, this asymmetry plays a key role in many cellular processes, including membrane trafficking and autophagy.
A new publication by Toshihide Kobayashi's group in the BIMC team, led by Yves Mély, demonstrates that sphingomyelin (SM), a lipid synthesized on the luminal side of the trans-Golgi network (TGN), is exposed on its cytoplasmic surface by the action of the protein GGA1 (Golgi-localized, gamma-adaptin ear-containing, ARF-binding protein 1).
Their results highlight that:
• The GAT domain of GGA1 induces a rearrangement of lipids depending on membrane curvature and the presence of cholesterol.
• This exposure of SM coincides with the release of mannose-6-phosphate (M6P) receptors from the TGN, a process essential for lysosomal enzyme trafficking.
• Furthermore, SM is transferred to autophagic membranes, where it facilitates autophagosome-lysosome fusion, a crucial step in the degradation of cellular components.
These results reveal a previously unrecognized role of lipid remodeling in the regulation of membrane trafficking and autophagy. They open new avenues for understanding the molecular mechanisms underlying these fundamental cellular processes.
Congratulations to all the authors !
Link : DOI: 10.1126/sciadv.aec4519
