Scientists found that endosomes participate in controlling the liver metabolism

Early endosomes are defined at the molecular level by the presence of a protein, small GTPase Rab5, which together with its effector molecules controls the fusion, motility and maturation of endosomes.

  • Scientists from the Virtual Liver Network (Zerial lab at the Max-Planck Institute MPI-CBG) recently showed that Rab5 is necessary for the biogenesis (de novo production) of the endo-lysosomal system, since depletion of this protein led to the loss of the degradative pathway. In addition scientists observed severe alterations in the hepatocellular metabolism.
  • An impaired function of a central metabolic organ such as the liver often triggers metabolic diseases such as biliary stasis, insulin resistance in diabetes, or high cholesterol levels. The reduction in Rab5 expression led to a rapid decrease of LDL (low-density lipoprotein) absorption by the liver cells and resulted in a ten-fold increase in serum cholesterol. This phenotype corresponds to the pathological symptoms of hypercholesterolemia.
  • Surprisingly, the reduction in Rab5 concentration and the subsequent loss of endosomes caused glucose storage in hepatocytes and formation of intracellular fat droplets. Recent evidence suggests that endosomes participate in controlling the expression of an important gene in glucose production by altering transcription factor activities. These results point to a previously unknown function of endosomes in the regulation of the sugar and fat metabolism.
  • The image shows the loss of early endosomes, which leads to pathological conditions in liver cells. Under physiological conditions the liver cell consists of a normal endo-lysosomal system that mediates the uptake of LDL into hepatocytes. Upon loss of Rab5 the endo-lysosomal system is reduced in number and the internalization of LDL is perturbed leading to hypercholesterolemia. In addition, accumulations of lipid droplets and glycogen granules are observed. This hints towards a misbalance in glucose and lipid metabolism.
  • Scientific publication: Rab5 is necessary for the biogenesis of the endolysosomal system in vivo. Nature. 2012.
  • Authors of text and image: Anja Zeigerer and Marino Zerial

  • Comprehensibility: 
    No votes yet
    (1=bad 5=excellent)