Bile acids are essential signaling molecules derived from cholesterol metabolism in the liver and are crucial for the digestion and absorption of fats. These molecules undergo further modification in the intestines by the gut microbiome . However, disruptions in bile flow, a condition known as cholestasis, can lead to the pathological accumulation of hydrophobic BAs in the liver and bloodstream.
This accumulation not only exacerbates liver damage but also induces significant disturbances in cellular processes. The review focuses on recent developments in understanding how BAs contribute to liver injury by affecting mitochondrial function, endoplasmic reticulum (ER) stress, inflammation, and autophagy. Pathways of hepatocyte apoptosis Mitochondria are central to the regulation of apoptosis, the programmed cell death process, which plays a pivotal role in cholestatic liver injury.
The review discusses two primary apoptotic pathways influenced by BAs: death receptor-independent and death receptor-dependent pathways. In death receptor-independent pathways, BAs can directly impair the mitochondrial electron transport chain (ETC), leading to the production of reactive oxygen species (ROS) and oxidative stress. This stress causes the mitochondrial permeability transition pore (mPTP) to open, disrupting the mitochondrial membrane potential and ultimately leading to cell death.
The release of cytochrome C from mitochondria into the cytosol triggers the intrinsic pathway of apoptosis, .