scholarly journals Structure and function of the voltage dependent anion channel

2010 ◽  
Vol 1797 ◽  
pp. 66 ◽  
Author(s):  
Sebastian Hiller ◽  
Thomas Raschle ◽  
Tsyr-Yan Yu ◽  
Amanda J. Rice ◽  
Thomas Walz ◽  
...  
Keyword(s):  
Anion Channel ◽  
Structure And Function ◽  
Voltage Dependent Anion Channel ◽  
Voltage Dependent ◽  
And Function

VDAC1 cysteine residues: topology and function in channel activity and apoptosis

2010 ◽  
Vol 427 (3) ◽  
pp. 445-454 ◽  
Author(s):  
Lior Aram ◽  
Shay Geula ◽  
Nir Arbel ◽  
Varda Shoshan-Barmatz
Keyword(s):  
Apoptotic Cell ◽  
Anion Channel ◽  
Cross Linking ◽  
Cysteine Residues ◽  
Channel Activity ◽  
Voltage Dependent Anion Channel ◽  
Oxidation Reduction ◽  
Voltage Dependent ◽  
And Function ◽  
Interfering Rna

The VDAC (voltage-dependent anion channel) is proposed to control metabolic cross-talk between mitochondria and the cytosol, as well as apoptotic cell death. It has been suggested that apoptosis is modulated by the oxidation state of VDAC. Since cysteine residues are the major target for oxidation/reduction, we verified whether one or both VDAC1 cysteine residues are involved in VDAC1-mediated transport or apoptosis activities. To assess the function of VDAC1 cysteine residues in channel activity and to probe cysteine topology with respect to facing the pore or the bilayer, we used thiol-modifying agents, namely membrane-permeable NEM (N-ethylmaleimide), bulky charged 5-FM (fluorescein-5-maleimide) and the cross-linking reagent BMOE [bis(maleimido)ethane]. Bilayer-reconstituted VDAC conductance was decreased by 5-FM, but not by NEM, whereas 5-FM had no effect on NEM-labelled VDAC conductance. BMOE caused the formation of dimeric VDAC1, suggesting that one of the two VDAC1 cysteine residues is exposed and available for cross-linking. The results thus suggest that one of the VDAC1 cysteine residues faces the VDAC pore, whereas the second is oriented towards the lipid bilayer. Mutated rat VDAC1 in which the two cysteine residues, Cys127 and Cys232, were replaced by alanine residues showed channel activity like native VDAC1 and, when expressed in cells, was localized to mitochondria. Human VDAC1-shRNA (small hairpin RNA)- or -siRNA (small interfering RNA)-treated cells, expressing low levels of endogenous human VDAC1 together with native or cysteine-less rat VDAC1, undergo apoptosis as induced by overexpression of these VDAC1 or upon treatment with reactive oxygen species-producing agents, H2O2, As2O3 or selenite, suggesting that the two cysteine residues are not required for apoptosis or VDAC1 oligomerization.

Porins in prokaryotes and eukaryotes: common themes and variations

2010 ◽  
Vol 431 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Kornelius Zeth ◽  
Marcus Thein
Keyword(s):  
Anion Channel ◽  
Gram Negative Bacteria ◽  
Molecular Architecture ◽  
Voltage Dependent Anion Channel ◽  
Mitochondrial Porin ◽  
Outer Membranes ◽  
Porin Protein ◽  
Outer Membrane Porin ◽  
Voltage Dependent ◽  
And Function

Gram-negative bacteria and mitochondria are both covered by two distinct biological membranes. These membrane systems have been maintained during the course of evolution from an early evolutionary precursor. Both outer membranes accommodate channels of the porin family, which are designed for the uptake and exchange of metabolites, including ions and small molecules, such as nucleosides or sugars. In bacteria, the structure of the outer membrane porin protein family of β-barrels is generally characterized by an even number of β-strands; usually 14, 16 or 18 strands are observed forming the bacterial porin barrel wall. In contrast, the recent structures of the mitochondrial porin, also known as VDAC (voltage-dependent anion channel), show an uneven number of 19 β-strands, but a similar molecular architecture. Despite the lack of a clear evolutionary link between these protein families, their common principles and differences in assembly, architecture and function are summarized in the present review.

scholarly journals Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore

2016 ◽  
Vol 113 (28) ◽  
pp. 7828-7833 ◽  
Author(s):  
Joseph R. Marquardt ◽  
Jennifer L. Perkins ◽  
Kyle J. Beuoy ◽  
Harold A. Fisk
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Anion Channel ◽  
Voltage Dependent Anion Channel ◽  
Monopolar Spindle ◽  
N Terminus ◽  
Voltage Dependent ◽  
And Function ◽  
Necessary And Sufficient ◽  
Spindle Function

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus.

scholarly journals VDAC1 in the diseased myocardium and the effect of VDAC1-interacting compound on atrial fibrosis induced by hyperaldosteronism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hadar Klapper-Goldstein ◽  
Ankit Verma ◽  
Sigal Elyagon ◽  
Roni Gillis ◽  
Michael Murninkas ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Apoptotic Cell ◽  
Anion Channel ◽  
Immunohistochemical Analysis ◽  
Voltage Dependent Anion Channel ◽  
Cardiac Tissues ◽  
Therapeutic Implications ◽  
Voltage Dependent ◽  
Models Of Lupus

AbstractThe voltage-dependent anion channel 1 (VDAC1) is a key player in mitochondrial function. VDAC1 serves as a gatekeeper mediating the fluxes of ions, nucleotides, and other metabolites across the outer mitochondrial membrane, as well as the release of apoptogenic proteins initiating apoptotic cell death. VBIT-4, a VDAC1 oligomerization inhibitor, was recently shown to prevent mitochondrial dysfunction and apoptosis, as validated in mouse models of lupus and type-2 diabetes. In the present study, we explored the expression of VDAC1 in the diseased myocardium of humans and rats. In addition, we evaluated the effect of VBIT-4 treatment on the atrial structural and electrical remodeling of rats exposed to excessive aldosterone levels. Immunohistochemical analysis of commercially available human cardiac tissues revealed marked overexpression of VDAC1 in post-myocardial infarction patients, as well as in patients with chronic ventricular dilatation\dysfunction. In agreement, rats exposed to myocardial infarction or to excessive aldosterone had a marked increase of VDAC1 in both ventricular and atrial tissues. Immunofluorescence staining indicated a punctuated appearance typical for mitochondrial-localized VDAC1. Finally, VBIT-4 treatment attenuated the atrial fibrotic load of rats exposed to excessive aldosterone without a notable effect on the susceptibility to atrial fibrillation episodes induced by burst pacing. Our results indicate that VDAC1 overexpression is associated with myocardial abnormalities in common pathological settings. Our data also indicate that inhibition of the VDAC1 can reduce excessive fibrosis in the atrial myocardium, a finding which may have important therapeutic implications. The exact mechanism\s of this beneficial effect need further studies.

scholarly journals Identification of two voltage-dependent anion channel-like protein sequences conserved in Kinetoplastida

2012 ◽  
Vol 8 (3) ◽  
pp. 446-449 ◽  
Author(s):  
Nadine Flinner ◽  
Enrico Schleiff ◽  
Oliver Mirus
Keyword(s):  
Outer Membrane ◽  
Trypanosoma Brucei ◽  
Protein Sequences ◽  
Anion Channel ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
Voltage Dependent

The eukaryotic porin superfamily consists of two families, voltage-dependent anion channel (VDAC) and Tom40, which are both located in the mitochondrial outer membrane. In Trypanosoma brucei , only a single member of the VDAC family has been described. We report the detection of two additional eukaryotic porin-like sequences in T. brucei . By bioinformatic means, we classify both as putative VDAC isoforms.

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