VPS13D: A Crucial Regulator of Organelle Contact Sites and Lipid Metabolism in Alcohol-Associated Steatohepatitis

Highlight

– VPS13D expression is reduced in human alcohol-associated hepatitis (AH) and correlates with decreased mitochondria-ER contact sites.
– Liver-specific deletion of Vps13d in mice exacerbates ethanol-induced steatosis, inflammation, and liver injury.
– VPS13D deficiency disrupts mitochondrial-ER and peroxisomal contacts, increases lysosomal damage and ER stress, and alters hepatic phospholipid metabolism.
– Impaired phosphatidylcholine synthesis via decreased PEMT expression leads to reduced VLDL secretion, promoting hepatic lipid accumulation.
– Adenoviral restoration of PEMT in Vps13d-deficient livers rescues VLDL secretion and ameliorates steatosis and liver injury.

Study Background