Isoforms of voltage-dependent anion channel of the outer mitochondrial membrane and experimental models to study their physiological role

Abstract

The review outlines our current understanding of the role of porins, the proteins forming voltage-dependent anion channels (VDAC), in regulation of permeability of the outer mitochondrial membrane. Recent data on the porin structure, amino acid sequence, and isoforms are discussed. The existence of three different VDAC isoforms in mammalian cells suggests that each isoform may play a specific physiological role that remains unknown so far. Different model systems and methods used for studies of functional differences between VDAC isoforms are overviewed. Particular attention is paid to studies of mammalian VDAC isoforms by means of expression of the corresponding genes in yeast and human cells as well as creation of stem cell clones and animals with genetically deficient isoforms of VDAC. It is concluded that permeability of the outer membrane plays a crucial role in the mechanisms of metabolic regulation and that porins are vitally important in the physiology of mammals. The data on the functional role of the VDAC isoforms can be useful for under-standing the mechanisms of such pathologies as cancer, diabetes, and neuromuscular diseases.