Modulation of Mitochondrial Voltage Dependent Anion Channel: Studies on Bilayer Electrophysiology

Daniel Tuikhang Koren^1,2Chetan Malik^3,4Shumaila Iqbal Siddiqui^3,4Rajan Shrivastava^5,6Subhendu Ghosh^3,4*

• ¹University of California Irvine School of Medicine, Irvine, United States
• ²University of California Irvine Department of Physiology and Biophysics, Irvine, United States
• ³University of Delhi, New Delhi, India
• ⁴University of Delhi - South Campus, New Delhi, India
• ⁵Vellore Institute of Technology, Vellore, India
• ⁶VIT University School of Computer Science and Engineering, Vellore, India

The present paper is a review of the mitochondrial Voltage Dependent Anion Channel (VDAC), popularly known as mitochondrial porin, which is a protein that forms a passive diffusion ion channel across the outer membrane of the mitochondrion. VDAC essentially plays an important role in the transport of metabolites like ATP between the intermembrane space of the mitochondrion and the cytoplasm. However, under certain conditions, it can give rise to cellular dysfunction, e.g., apoptosis. Although VDAC is present in all eukaryotic cells, this review has focused mainly on the animal tissues. Interactions of VDAC with various enzymes, proteins, and small molecules or ligands have been reviewed with a perspective of bilayer electrophysiology. Importantly, the biochemical (post-translational) modifications of the channel protein, namely phosphorylation (by a series of kinases), acetylation, ubiquitination, oxidative modifications (such as glutathionylation and nitrosylation), etc., and their impact on the electrophysiological properties have been discussed. Finally, the consequences of the above-mentioned experimental findings have been discussed with predictions and hypotheses relevant to living systems.