Renaissance of VDAC: New Insights on a Protein Family at the Interface between Mitochondria and Cytosol

Abstract

It has become impossible to review all the existing literature on Voltage-Dependent Anion selective Channel (VDAC) in a single article. A real Renaissance of studies brings this protein to the center of decisive knowledge both for cell physiology and therapeutic application. This review, after highlighting the similarities between the cellular context and the study methods of the solute carriers present in the inner membrane and VDAC in the outer membrane of the mitochondria, will focus on the isoforms of VDAC and their biochemical characteristics. In particular, the possible reasons for their evolutionary onset will be discussed. The variations in their post-translational modifications and the differences between the regulatory regions of their genes, probably the key to understanding the current presence of these genes, will be described. Finally, the situation in the higher eukaryotes will be compared to that of yeast, a unicellular eukaryote, where there is only one active isoform and the role of VDAC in energy metabolism is better understood.

Keywords: Voltage-Dependent Anion selective Channel; bioenergetics; gene promoter; isoforms; metabolism; oxidative post-translational modification; yeast.

Figure 1

Secondary structure elements and cysteines localization in a multi-alignment of human Voltage-Dependent Anion selective Channel (VDAC) isoforms. Color code: light blue: β-strands; green: loops exposed to cytosol; orange: the N-terminal sequence containing α-helical portions; no color: loops exposed to inter-membrane space. Cysteine residues of VDAC2 and VDAC3 are in red and highlighted in yellow; red arrows point cysteine residues exposed to inter-membrane space (Figure obtained with the support of F. Zinghirino).