VDAC isoforms in mammals

VDACs (Voltage Dependent Anion selective Channels) are a family of pore-forming proteins discovered in the mitochondrial outer membrane. In the animal kingdom, mammals show a conserved genetic organization of the VDAC genes, corresponding to a group of three active genes. Three VDAC protein isoforms thus exist. From a historically point of view most of the data collected about this protein refer to the VDAC1 isoform, the first to be identified and also the most abundant in the organisms. In this work we compare the information available about the three VDAC isoforms, with a special emphasis upon the human proteins, here considered prototypical of the group, and we try to shed some light on specific functional roles of this apparently redundant group of proteins. A new hypothesis about the VDAC(s) involvement in ROS control is proposed. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.

► VDAC isoforms in eutheria are a well conserved family of outer membrane mitochondrial protein.
► The 3 VDAC isoforms in mitochondria have distinct roles in the cell.
► VDAC1 is the most abundant pore, pro-apoptotic and specific for low amplitude Ca2+ signals.
► VDAC2 has a longer N-end, similar activity than VDAC1 and is considered anti-apoptotic.
► VDAC3 is the least known, has a poor pore-forming activity and additional functions in cell.