Longevity & AgingScientists Discover LYVAC Protein That Drives Lysosomal Swelling in Disease
Researchers at the University of Pittsburgh identified LYVAC (formerly PDZD8), an ER-anchored lipid transfer protein, as a master mediator of lysosomal vacuolation — the abnormal swelling of lysosomes seen in aging, neurodegeneration, infection, and cancer. Using proximity proteomics, knockout models, and lipid imaging, they showed that diverse stressors converge on lysosomal osmotic stress, triggering LYVAC recruitment to ER-lysosome contact sites. Once recruited, LYVAC transfers lipids — particularly phosphatidylserine and cholesterol — from the ER to the lysosome, enabling membrane expansion. The findings establish LYVAC as a general sensor-executor of lysosomal osmotic stress and reveal a previously unknown mechanism underlying a hallmark of cellular pathology.
