VDAC Structure and Function: an Up-to-Date View

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About this Research Topic

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Background

VDAC (Voltage Dependent Anion-selective Channel) is the channel protein allowing the permeability of the outer mitochondrial membrane. This main function has been characterized many years ago, but how this function is eventually modulated and modified by external or mitochondrial stimuli is still a matter of debate. The structure of the pore has been obtained already in 2008, showing a new, peculiar organization of the transmembrane pore. This structure was proposed to be essentially identical for any of the VDAC isoforms known, but, again, its modifications as a result of biochemical actions is not yet defined. Structure and function of this protein are thus the two challenges that we have to face to fully understand the role of this structure in the cell.

The Research Topic will present the most recent contributions and points of view about the investigations regarding the identification of potential active or binding-sites in the protein, chemico-physical modifications of its structure with consequences and fallouts in the function of the pore, or, conversely, about cellular of physiological inputs that can have effects on the structure.
Several investigators are now exploring this at a molecular level and with the aims of elucidating the intimate mechanisms, the presence of specific binding sites for nucleotides or new drugs, for proteins or peptides.
Another relevant field is the knowledge of the protein dynamics involved in the voltage-dependence switch, that is only known as an electrophysiological phenomenon in artificial membrane systems but that is of the outmost importance when defined in the context of the living cell. The post-translational modifications that VDAC undergoes in the bioenergetics context of the mitochondria and their consequences on the quality control of the protein and of the whole outer membrane are also a relevant subtopic. The targeting of the VDAC to the outer mitochondrial membrane has been recently studied and a proposal about the determinants of its action proposed.

This Research Topic is aimed to build a collection of contributions well focused on the state-of-the-art of the structural and functional knowledge of VDAC. This means that primarily research articles will be welcome, but also mini-reviews on sharp and specific aspects will be considered.

The main reason is the present lack of an organized view about VDAC: many times, in the past, laboratories working on other subjects or pathways incidentally fell in this protein, which is pretty abundant in the cell and with special physico-chemical features. It is now time to build a unified description of the matter, by joining the contributions of the main laboratories in the world which devoted their efforts into this fascinating protein.

Keywords: VDAC, mitochondrial outer membrane, structure, voltage sensor, N-terminal end

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