Preferences help
enabled [disable] Abstract
Number of results
2003 | 50 | 2 | 415-424
Article title

Modulation of the voltage-dependent anion-selective channel by cytoplasmic proteins from wild type and the channel depleted cells of Saccharomyces cerevisiae.

Title variants
Languages of publication
It is well known that effective exchange of metabolites between mitochondria and the cytoplasm is essential for cell physiology. The key step of the exchange is transport across the mitochondrial outer membrane, which is supported by the voltage-dependent anion-selective channel (VDAC). Therefore, it is clear that the permeability of VDAC must be regulated to adjust its activity to the actual cell needs. VDAC-modulating activities, often referred to as the VDAC modulator, were identified in the intermembrane space of different organism mitochondria but the responsible protein(s) has not been identified as yet. Because the VDAC modulator was reported to act on VDAC of intact mitochondria when added to the cytoplasmic side it has been speculated that a similar modulating activity might be present in the cytoplasm. To check the speculation we used mitochondria of the yeast Saccharomyces cerevisiae as they constitute a perfect model to study VDAC modulation. The mitochondria contain only a single isoform of VDAC and it is possible to obtain viable mutants devoid of the channel (Δpor1). Moreover, we have recently characterised a VDAC-modulating activity located in the intermembrane space of wild type and Δpor1 S. cerevisiae mitochondria. Here, we report that the cytoplasm of wild type and Δpor1 cells of S. cerevisiae contains a VDAC-modulating activity as measured in a reconstituted system and with intact mitochondria. Since quantitative differences were observed between the modulating fractions isolated from wild type and Δpor1 cells when they were studied with intact wild type mitochondria as well as by protein electrophoresis it might be concluded that VDAC may influence the properties of the involved cytoplasmic proteins. Moreover, the VDAC-modulating activity in the cytoplasm differs distinctly from that reported for the mitochondrial intermembrane space. Nevertheless, both these activities may contribute efficiently to VDAC regulation. Thus, the identification of the proteins is very important.
Physical description
  • Antos N, Budzinska M, Kmita, H. (2001) An interplay between the TOM complex and porin isoforms in the yeast Saccharomyces cerevisiae mitochondria. . FEBS Lett.; 500: 12-6.
  • Benz R. (1994) Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins. . Biochim Biophys Acta.; 1197: 167-96.
  • Benz R, Janko K, Boos W, Lauger P. (1978) Formation of large, ion-permeable membrane channels by the matrix protein (porin) of Escherichia coli. . Biochim Biophys Acta.; 511: 305-19.
  • Blachy-Dyson E, Forte M. (2001) VDAC channels. . IUBMB Life.; 52:113-8.
  • Blachly-Dyson E, Song J, Wolfgang WJ, Colombini M, Forte M. (1997) Multicopy suppressors of phenotype resulting from the absence of yeast VDAC encode a VDAC-like protein. . Mol Cell Biol.; 17: 5727-38.
  • Blachly-Dyson E, Zambrowicz EB, Yu WH, Adams V, McCabe ERB, Adelman J, Colombini M, Forte M. (1993) Cloning and functional expression in yeast of two human isoforms of the outer mitochondrial membrane channel, the voltage-dependent anion channel. . J Biol Chem.; 268: 1835-41.
  • Colombini M. (1979) A candidate for the permeability pathway of the outer mitochondrial membrane. . Nature.; 279: 643-5.
  • Colombini M. (1994) Anion channels in the mitochondrial outer membrane. . Curr Top Membr.; 42: 73-101.
  • Colombini M, Blachly-Dyson E, Forte, M. (1996) VDAC, a channel in the outer mitochondrial membrane. In Ion Channels. Narahashi T. ed, pp 169-201. Plenum Press, New York.
  • Crompton M, Barksby E, Johnson N, Capano M. (2002) Mitochondrial intermembrane junctional complexes and their involvement in cell death. . Biochimie; 84: 143-52.
  • Daum G, Bohni PC, Schatz G. (1982). Import of proteins into mitochondria. Cytochrome b2 and cytochrome c peroxidase are located in the intermembrane space of yeast mitochondria. . J Biol Chem.; 257: 13028-33.
  • De Pinto V, Ludwig O, Krause J, Benz R, Palmieri F. (1987) Porin pores of mitochondrial outer membranes from high and low eukaryotic cells: biochemical and biophysical characterization. . Biochim Biophys Acta.; 894: 109-19.
  • De Vries S, Marres CA. (1987) The mitochondrial respiratory chain of yeast. Structure and biosynthesis and the role in cellular metabolism. . Biochim Biophys Acta.; 895: 205-39.
  • Douce R, Bourguignon R, Neuberger M. (1984) Isolation of plant mitochondria. General principles and criteria of integrity. . Meth Enzymol.; 148: 403-15.
  • Elkeles A, Breiman A, Zizi M. (1997) Functional differences among wheat voltage-dependent anion channel (VDAC) isoforms expressed in yeast. Indication for the presence of a novel VDAC-modulating protein? . J Biol Chem.; 272: 6252-60.
  • Heins L, Mentzel H, Schmid A, Benz R, Schmitz UK. (1994) Biochemical, molecular, and functional characterization of porin isoforms from potato mitochondria. . J Biol Chem.; 269: 26402-10.
  • Holden MJ, Colombini M. (1988) The mitochondrial outer membrane channel, VDAC, is modulated by a soluble protein. . FEBS Lett.; 241: 105-9.
  • Holden MJ, Colombini M. (1993) The outer mitochondrial membrane channel, VDAC, is modulated by a protein localized in the intermembrane space. . Biochim Biophys Acta.; 1144: 396-402.
  • Kamo N, Muratsugu M, Hongoh R, Kobatake YJ (1979) Membrane potential of mitochondria measured with electrode sensitive to tetraphenyl phosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state. . J Membr Biol.; 49: 105-21.
  • Kmita H, Budzinska M. (2000) Involvement of the TOM complex in external NADH transport into yeast mitochondria depleted of mitochondrial porin1. . Biochim Biophys Acta.; 1509: 86-94.
  • Laemmli UK. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. . Nature.; 227: 680-5.
  • Lee AC, Xu X, Blachly-Dyson E, Forte M, Colombini M. (1998) The role of yeast VDAC genes on the permeability of the mitochondrial outer membrane. . J Membr Biol.; 161: 173-81.
  • Lemeshko VV. (2002) Model of the outer membrane potential generation by the inner membrane of mitochondria. . Biophys J.; 82: 684-92.
  • Liu MY, Colombini M. (1991) Voltage gating of the mitochondrial outer membrane channel VDAC is regulated by a very conserved protein. . Am J Physiol.; 260: C371-4.
  • Liu MY, Colombini M. (1992) Regulation of mitochondrial respiration by controlling the permeability of the outer membrane through the mitochondrial channel, VDAC. . Biochim Biophys Acta.; 1098: 255-60.
  • Liu MY, Torgrimson A, Colombini M. (1994) Characterization and partial purification of the VDAC-channel-modulating protein from calf liver mitochondria. . Biochim Biophys Acta.; 1185: 203-12.
  • Michejda J, Kmita H, Stobienia O, Budzinska M, Lauquin GJ-M. (1994) Restriction of metabolite permeation through the outer mitochondrial membrane of porin-deficient yeast mutant. In: molecular biology of mitochondrial transport system. Forte M, Colombini M. eds, pp 341-56. Springer-Verlag, Heidelberg.
  • Sampson MJ, Lovell RS, Craigen WJ. (1997) The murine voltage-dependent anion channel gene family. Conserved structure and function. . J Biol Chem.; 272: 18966-73.
  • Schein SJ, Colombini M, Finkelstein A. (1976) Reconstitution in planar lipid bilayers of a voltage-dependent anion-selective channel. . J Membr Biol.; 30: 99-120.
  • Shimizu S, Ide T, Yanagida T, Tsujimoto Y. (2000) Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c. . J Biol Chem.; 275: 12321-5.
  • Stobienia O, Wroblewska S, Antos N, Budzinska M, Kmita H. (2002) The key role of the energized state of Saccharomyces cerevisiae mitochondria in modulations of the outer membrane channels by the intermembrane space proteins. . J Bioenerg Biomembr.; 34: 507-16.
  • Tsujimoto Y, Shimizu S. (2002) The voltage-dependent anion channel: an essential player in apoptosis. . Biochimie.; 84: 187-93.
  • Vander Heiden MG, Chandel NS, Li XX, Schumacker PT, Colombini M, Thompson CB. (2000) Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival. Proc Natl Acad Sci U S A.; 97: 4666-71.
  • Vander Heiden MG, Chandel NS, Schumacker PT, Thompson CB (1999) Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange. . Mol Cell.; 3: 159-67.
  • Xu X, Decker W, Sampson MJ, Craigen WJ, Colombini M. (1999) Mouse VDAC isoforms expressed in yeast: channel properties and their roles in mitochondrial outer membrane permeability. J Membr Biol.; 170: 89-102.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.