The Impact of Mitochondrial Dysfunction on Enterocyte Lipid Processing

Mitochondrial dysfunction in enterocytes, caused by DARS2 deficiency, leads to impaired processing and transport of dietary lipids, resulting in their accumulation within large lipid droplets (LDs). This study found that mice lacking DARS2 specifically in enterocytes showed severe intestinal pathology, including reduced body weight, impaired tissue architecture, and decreased cell proliferation. The enterocytes of these mice contained large LDs filled with lipids, while the livers showed reduced levels of lipids. Similar lipid accumulation and pathology were observed in mice lacking specific subunits of respiratory chain complexes II and IV. Inducible DARS2 ablation in adult mice also resulted in lipid accumulation in enterocytes. These findings suggest that mitochondrial dysfunction in enterocytes disrupts the processing and transport of dietary lipids, leading to their accumulation in LDs.