title: Regulation of respiration in muscle cells in vivo by VDAC through interaction with the cytoskeleton and MtCK within Mitochondrial Interactosome.
abstract: This review describes the recent experimental data on the importance of the VDAC-cytoskeleton interactions in determining the mechanisms of energy and metabolite transfer between mitochondria and cytoplasm in cardiac cells. In the intermembrane space mitochondrial creatine kinase connects VDAC with adenine nucleotide translocase and ATP synthase complex, on the cytoplasmic side VDAC is linked to cytoskeletal proteins. Applying immunofluorescent imaging and Western blot analysis we have shown that β2-tubulin coexpressed with mitochondria is highly important for cardiac muscle cells mitochondrial metabolism. Since it has been shown by Rostovtseva et al. that αβ-heterodimer of tubulin binds to VDAC and decreases its permeability, we suppose that the β-tubulin subunit is bound on the cytoplasmic side and α-tubulin C-terminal tail is inserted into VDAC. Other cytoskeletal proteins, such as plectin and desmin may be involved in this process. The result of VDAC-cytoskeletal interactions is selective restriction of the channel permeability for adenine nucleotides but not for creatine or phosphocreatine that favors energy transfer via the phosphocreatine pathway. In some types of cancer cells these interactions are altered favoring the hexokinase binding and thus explaining the Warburg effect of increased glycolytic lactate production in these cells. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.
authors.affiliation: INSERM U1055, Laboratory of Fundamental and Applied Bioenergetics, Joseph Fourier University, Grenoble, France. rita.guzun@gmail.com
authors.forename: Rita
authors.initials: R
authors.lastname: Guzun
authors.forename: Marcela
authors.initials: M
authors.lastname: Gonzalez-Granillo
authors.forename: Minna
authors.initials: M
authors.lastname: Karu-Varikmaa
authors.forename: Alexei
authors.initials: A
authors.lastname: Grichine
authors.forename: Yves
authors.initials: Y
authors.lastname: Usson
authors.forename: Tuuli
authors.initials: T
authors.lastname: Kaambre
authors.forename: Karen
authors.initials: K
authors.lastname: Guerrero-Roesch
authors.forename: Andrey
authors.initials: A
authors.lastname: Kuznetsov
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlattner
authors.forename: Valdur
authors.initials: V
authors.lastname: Saks
mesh_terms: D000818:Animals; D019069:Cell Respiration; D052281:Creatine Kinase, Mitochondrial Form / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D032342:Muscle Cells / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
chemical_list: D050994:Voltage-Dependent Anion Channels; D052281:Creatine Kinase, Mitochondrial Form