Tubulin C-terminal tail-Voltage-dependent anion channel interface (Tubulin-VDAC interface) (Tubulin-VDAC interface)

The Tubulin C-terminal tail (CTT)-Voltage-dependent anion channel (VDAC) interface represents a critical regulatory checkpoint in cellular bioenergetics and metabolic signaling. Tubulin CTTs are intrinsically disordered, negatively charged regions that project from the microtubule surface or free tubulin dimers and physically interact with VDAC on the outer mitochondrial membrane (Rostovtseva & Bezrukov, 2008). This interaction results in a reversible blockade of the VDAC pore, significantly reducing the conductance of ATP, ADP, and other respiratory metabolites between the mitochondria and the cytoplasm (Gurnev et al., 2011). Beyond VDAC, tubulin CTTs also serve as docking sites for various glycolytic and metabolic enzymes, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase (LDH), thereby modulating their enzymatic activity and spatial organization within the cell (Monge et al., 2008). In malignant cells, the high concentration of free dimeric tubulin leads to persistent VDAC closure, which suppresses mitochondrial oxidative phosphorylation and promotes the Warburg effect (Maldonado et al., 2013). Conversely, in neurodegenerative diseases, alterations in tubulin post-translational modifications can disrupt this interface, contributing to mitochondrial dysfunction and energy failure. Therapeutic targeting of this interface, using small molecules like erastin or specific mimetic peptides, offers a novel approach to reprogram cancer metabolism or protect neuronal health by modulating mitochondrial metabolite flux.

Other names

Tubulin-VDAC interactionTubulin-mitochondrial interfaceTubulin-metabolic enzyme complexVDAC-tubulin regulatory site

Modulation of the physical blockade of the VDAC pore by tubulin C-terminal tails to regulate mitochondrial metabolite flux and membrane potential.