STARD1 promotes cholestatic liver injury and disease progression

Yes, STARD1 (Steroidogenic Acute Regulatory Protein D1) plays a key role in promoting cholestatic liver injury and disease progression. Cholestatic liver diseases occur when bile acids, which are made from cholesterol, build up in the liver cells (hepatocytes). This buildup causes liver damage, inflammation, scarring (fibrosis), and can eventually lead to cirrhosis.

STARD1 is a protein that helps transport cholesterol into mitochondria, where it can be used to make bile acids through a specific pathway. However, too much mitochondrial cholesterol, facilitated by STARD1, disrupts the liver’s natural defenses against oxidative stress. This makes the liver more vulnerable to damage from toxic bile acids.

Studies in mice have shown that removing STARD1 specifically from liver cells (Stard1^Δhep^ mice) protects them from cholestatic injury. These mice had lower levels of harmful bile acids and mitochondrial cholesterol, less oxidative stress, and better antioxidant defenses, particularly higher levels of mitochondrial glutathione (mGSH). As a result, they experienced less liver inflammation and fibrosis compared to normal mice.

In humans, patients with primary biliary cholangitis (PBC), a type of cholestatic liver disease, show higher levels of STARD1 in their liver, linking it to disease severity. Targeting STARD1 or its effects on mitochondrial cholesterol and glutathione metabolism could be a promising treatment strategy for cholestatic liver diseases.