PLIN5 phosphorylation orchestrates mitochondria lipid-droplet coupling to control hepatic lipid flux and steatosis - PubMed
4 hours ago
- #PLIN5 phosphorylation
- #mitochondria-LD coupling
- #steatosis
- Steatotic liver disease mechanisms are unclear, especially how hepatocytes handle dietary fatty acid surges.
- Single-cell tissue imaging (scPhenomics) and spatial proteomics used to study lipid handling across dietary states.
- Fasting increases mitochondria-lipid droplet (LD) contacts, while Western diet (WD) reduces them in male mice.
- Fasting elevates perilipin-5 (PLIN5), which mediates mitochondria-LD tethering.
- PLIN5 phosphorylation modulates organelle contacts: S155A variant enhances contacts and LD expansion, S155E reduces contacts and LD size.
- S155A overexpression in WD reduces lipotoxicity.
- Adaptive organelle-interaction program channels lipids during nutrient stress, attenuated by obesogenic diets.
- scPhenomics enables spatially resolved cell-state analysis.
- PLIN5 phosphorylation identified as a therapeutic target for tuning hepatocyte lipid flux via mitochondria-LD coupling.