VDAC1-based peptide as potential treatment for pathologies of the liver and pancreas

Abstract

Diseases associated with damage to such vital organs of the digestive system as the liver and pancreas are an urgent problem of world health. Non-alcoholic fatty liver disease (NAFLD) is a worldwide epidemic; the problem of type 2 diabetes (T2D) mellitus becomes more acute every year; hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. In spite of progress in identifying risk factors, at the moment there is no generally accepted strategy for a complete cure for these pathologies. Mitochondria, with multiple functions, are key cell organelles. VDAC1, a channel in the outer membrane of mitochondria, is involved in the regulation of cell energy homeostasis, cellular stress, Ca2+ concentration, plays an important role in mitochondria-mediated apoptosis, and also interacts with more than 100 proteins. Numerous channel functions make peptides containing the VDAC1 sequence attractive for therapeutic use. In this article, we consider the VDAC1-based peptide (R-Tf-D-LP4) as a promising method for the treatment of metabolic disorders, and we present possible mechanisms by which the peptide affects the metabolism of fats and carbohydrates. R-Tf-D-LP4 is able to restore normal liver morphology (reducing manifestations of fatty degeneration of hepatocytes, inflammation and fibrosis), is able to slow down the growth of hepatocellular carcinoma by inducing apoptosis and bring blood glucose levels close to normal due to restoration of the normal morphological structure of the pancreas.

Keywords

• mitochondria
• vdac1
• r-tf-d-lp4
• non-alcoholic fatty liver disease
• hepatocellular carcinoma
• type 2 diabetes mellitus