Free tubulin modulates mitochondrial membrane potential in cancer cells.

ABSTRACT: Formation of the mitochondrial membrane potential (ΔΨ) depends on flux of respiratory substrates, ATP, ADP, and Pi through voltage-dependent anion channels (VDAC). As tubulin promotes single-channel closure of VDAC, we hypothesized that tubulin is a dynamic regulator of ΔΨ, which in cultured cancer cells was assessed by confocal microscopy of the potential-indicating fluorophore tetramethylrhodamine methylester (TMRM). Microtubule destabilizers, rotenone, colchicine, and nocodazole, and the microtubule stabilizer paclitaxel increased and decreased cellular free tubulin, respectively, and in parallel decreased and increased ΔΨ. Protein kinase A (PKA) activation by cAMP analogues and glycogen synthase kinase 3β (GSK-3β) inhibition decreased ΔΨ, whereas PKA inhibition hyperpolarized, consiste

SUBMITTER: Maldonado EN 

PROVIDER: S-EPMC3010233 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature