FGF21 regulation performs the potential biological roles in different tissues based on FGFR-βklotho signaling transduction, including participating in the glucose and lipid regulation, the improvement of hepatic steatosis, and anti-fibrotic effects in liver, improving damage and fibrosis in kidney, preventing ROS, cardiac hypertrophy, and atherosclerosis in heart, predicting mitochondrial disease in muscles, regulating insulin production in pancreas, and lipid regulation in adipose tissue. This evidence concerns the gene FGF21 and mitochondrial disease.