Studies on the isolated mitochondrial damage induced by α-tocopheryl succinate and its interactions with human serum albumin

Abstract

α-tocopheryl succinate (α-TOS), a redox-inactive vitamin E analogue, holds great promise for selectively triggering mitochondrial apoptosis in tumor cells. In this paper, in order to better understand the biophysical basis of α-TOS under biological conditions, the effects of α-TOS at high concentrations on the function of mitochondria and its interactions with human blood protein (human serum albumin, HSA) were investigated. We found that α-TOS with high concentration not only caused inhibition of mitochondrial respiration and mitochondrial permeability transition (MPT), but also strongly disturbed the mitochondrial membrane and ultrastructure. These results suggest that mitochondria are organelles that are very sensitive to α-TOS-induced stress, and the mechanism of damage to mitochondria may be due to MPT and impairing of the respiratory chain. In addition, it has been also demonstrated that α-TOS possesses moderate binding affinity to HSA in site I due to the formation of the α-TOS–HSA complex by hydrophobic, van der Waals and hydrogen bond forces. These results will help us learn more about biophysical properties of α-TOS at subcellular (mitochondria) and biomacromolecular (HSA) levels.