4.6 Review

Tubulin βII and βIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease

Journal

CELLS
Volume 8, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/cells8030239

Keywords

tubulin; voltage-dependent anion channel (VDAC); mitochondria; hexokinase; oxidative phosphorylation; creatine kinase; oxidative muscle; brain; synaptosomes; cancer

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Funding

  1. Estonian Ministry of Education and Research [IUT23-1]

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In recent decades, there have been several models describing the relationships between the cytoskeleton and the bioenergetic function of the cell. The main player in these models is the voltage-dependent anion channel (VDAC), located in the mitochondrial outer membrane. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. At the same time, high-energy phosphates are channeled out and directed to cellular energy transfer networks. Regulation of these energy fluxes is controlled by beta-tubulin, bound to VDAC. It is also thought that beta-tubulin-VDAC interaction modulates cellular energy metabolism in cancer, e.g., switching from oxidative phosphorylation to glycolysis. In this review we focus on the described roles of unpolymerized alpha beta-tubulin heterodimers in regulating VDAC permeability for adenine nucleotides and cellular bioenergetics. We introduce the Mitochondrial Interactosome model and the function of the beta II-tubulin subunit in this model in muscle cells and brain synaptosomes, and also consider the role of beta III-tubulin in cancer cells.

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