Abstract 1219: Tubulin binding to mitochondrial VDAC: A new regulator of oxidative metabolism and apoptosis? A new role for tubulin

Abstract

Abstract Tubulin binding to the outer mitochondrial membrane (OMM) was first reported many years ago but the function was unknown; we showed recently that dimeric tubulin binds to VDAC, the major metabolite channel in the OMM, and that this results in closing the channel to ATP-ADP exchange, with a consequent drop in oxidative phosphorylation. This could act as a regulator of normal oxidative metabolism, but excess tubulin binding could also lead to changes in the inner membrane potential, and possibly lead to mitochondrial swelling and triggering of apoptosis. To evaluate the plausibility of this mechanism for either regulation of normal metabolism or induction of apoptosis, the concentrations of tubulin and VDAC in the cell need to be known, as a huge discrepancy in either direction could make the mechanism unlikely. We have used semiquantitative Western blots to measure the concentrations of tubulin and VDAC in total cell extracts from a number of cancer cell lines. As expected, we found tubulin to be an abundant protein (∼0.5 % of total protein), but we also found VDAC to be more abundant than perhaps commonly thought (∼0.2 % of total protein). Thus we conclude that tubulin regulation of VDAC permeability is a plausible mechanism. Further experiments are underway to test this mechanism and its role in induction of apoptosis by chemotherapy agents, especially microtubule-directed ones. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1219.