Mitochondrial Dysfunction and Acute Fatty Liver of Pregnancy

The liver is one of the richest organs in mitochondria, serving as a hub for key metabolic pathways such as beta-oxidation, the tricarboxylic acid (TCA) cycle, ketogenesis, respiratory activity, and adenosine triphosphate (ATP) synthesis, all of which provide metabolic energy for the entire body. Mitochondrial dysfunction has been linked to subcellular organelle dysfunction in liver diseases, particularly fatty liver disease. Acute fatty liver of pregnancy (AFLP) is a life-threatening liver disorder unique to pregnancy, which can result in serious maternal and fetal complications, including death. Pregnant mothers with this disease require early detection, prompt delivery, and supportive maternal care. AFLP was considered a mysterious illness and though its pathogenesis has not been fully elucidated, molecular research over the past two decades has linked AFLP to mitochondrial dysfunction and defects in fetal fatty-acid oxidation (FAO). Due to deficient placental and fetal FAO, harmful 3-hydroxy fatty acid metabolites accumulate in the maternal circulation, causing oxidative stress and microvesicular fatty infiltration of the liver, resulting in AFLP. In this review, we provide an overview of AFLP and mitochondrial FAO followed by discussion of how altered mitochondrial function plays an important role in the pathogenesis of AFLP.

Automated summary

The liver is a highly mitochondrial-rich organ that plays a crucial role in various metabolic processes. Mitochondrial dysfunction is associated with liver diseases, particularly fatty liver disease. Acute fatty liver of pregnancy (AFLP) is a life-threatening liver disorder unique to pregnant women, and its pathogenesis has been linked to mitochondrial dysfunction and fetal fatty-acid oxidation defects. This review provides an overview of AFLP and mitochondrial fatty-acid oxidation, highlighting the importance of altered mitochondrial function in the development of AFLP.