Voltage-Dependent Anion Channel (VDAC) in Health and Disease

Abstract

Abstract The voltage-dependent anion channel (VDAC) is recognized as the key metabolite pathway of water-soluble metabolites, small ions, and polypeptides across the outer mitochondrial membrane. The significance of this relatively simple β-barrel channel arises from its crucial position at the interface between the mitochondria and the cytosol. Simultaneous access to strictly compartmentalized mitochondrial and cytosolic proteins endows VDAC with a unique regulatory role over the vital communications between mitochondria and the cytosol making VDAC an important cellular communication hub. VDAC has been implicated in a wide range of mitochondria-associated pathologies such as diabetes, cardiovascular diseases, various cancers, and neurodegenerative disorders. Therefore, understanding the molecular mechanism of VDAC functioning and identification of its natural regulators and synthetic inhibitors are vital for improving outcomes of mitochondria-associated diseases by using VDAC as a pharmacological target. This chapter provides an overview of VDAC channel biophysical properties and its role in mitochondrial metabolism, calcium homeostasis, and apoptosis with a focus on VDAC regulation by cytosolic proteins and lipids. VDAC’s role in different diseases and the current state of VDAC pharmacology are also discussed.