scholarly journals The Open State Selectivity of the Bean Seed VDAC Depends on Stigmasterol and Ion Concentration

2021 ◽  
Vol 22 (6) ◽  
pp. 3034
Author(s):  
Hayet Saidani ◽  
Marc Léonetti ◽  
Hanna Kmita ◽  
Fabrice Homblé
Keyword(s):  
Physiological Role ◽  
Anion Channel ◽  
Physiological Effect ◽  
Ion Concentration ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
Major Pathway ◽  
Voltage Dependent ◽  
State Selectivity

The voltage-dependent anion channel (VDAC) is the major pathway for metabolites and ions transport through the mitochondrial outer membrane. It can regulate the flow of solutes by switching to a low conductance state correlated with a selectivity reversal, or by a selectivity inversion of its open state. The later one was observed in non-plant VDACs and is poorly characterized. We aim at investigating the selectivity inversion of the open state using plant VDAC purified from Phaseolus coccineus (PcVDAC) to evaluate its physiological role. Our main findings are: (1) The VDAC selectivity inversion of the open state occurs in PcVDAC, (2) Ion concentration and stigmasterol affect the occurrence of the open state selectivity inversion and stigmasterol appears to interact directly with PcVDAC. Interestingly, electrophysiological data concerning the selectivity inversion of the PcVDAC open state suggests that the phenomenon probably does not have a significant physiological effect in vivo.

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.

scholarly journals Structure of the human voltage-dependent anion channel

2008 ◽  
Vol 105 (40) ◽  
pp. 15370-15375 ◽  
Author(s):  
Monika Bayrhuber ◽  
Thomas Meins ◽  
Michael Habeck ◽  
Stefan Becker ◽  
Karin Giller ◽  
...  
Keyword(s):  
Metabolic Flux ◽  
3D Structure ◽  
Anion Channel ◽  
Bioinformatic Analysis ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
X Ray Crystallography ◽  
Voltage Dependent ◽  
Α Helix ◽  
Induced Apoptosis

The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is the most abundant protein in the mitochondrial outer membrane (MOM). VDAC is the channel known to guide the metabolic flux across the MOM and plays a key role in mitochondrially induced apoptosis. Here, we present the 3D structure of human VDAC1, which was solved conjointly by NMR spectroscopy and x-ray crystallography. Human VDAC1 (hVDAC1) adopts a β-barrel architecture composed of 19 β-strands with an α-helix located horizontally midway within the pore. Bioinformatic analysis indicates that this channel architecture is common to all VDAC proteins and is adopted by the general import pore TOM40 of mammals, which is also located in the MOM.

Moving Ca2+ from the endoplasmic reticulum to mitochondria: is spatial intimacy enough?

2006 ◽  
Vol 34 (3) ◽  
pp. 351-355 ◽  
Author(s):  
G.A. Rutter
Keyword(s):  
Endoplasmic Reticulum ◽  
Outer Membrane Proteins ◽  
Anion Channel ◽  
Mitochondrial Outer Membrane ◽  
Interconnected Network ◽  
Voltage Dependent Anion Channel ◽  
Permeabilized Cells ◽  
Inositol 1,4,5 Trisphosphate ◽  
Voltage Dependent ◽  
Trisphosphate Receptor

A number of studies in recent years have demonstrated that the ER (endoplasmic reticulum) makes intimate contacts with mitochondria, the latter organelles existing both as individual organelles and occasionally as a more extensive interconnected network. Demonstrations that mitochondria take up Ca2+ more avidly upon its mobilization from the ER than when delivered to permeabilized cells as a buffered solution also indicate that a shielded conduit for Ca2+ may exist between the two organelle types, perhaps comprising the inositol 1,4,5-trisphosphate receptor and mitochondrial outer membrane proteins including the VDAC (voltage-dependent anion channel). Although the existence of such intracellular ER–mitochondria ‘synapses’, or of an ER–mitochondria Ca2+ ‘translocon’, is an exciting idea, more definitive experiments are needed to test this possibility.

scholarly journals Evolutionary selection of a 19-stranded mitochondrial β-barrel scaffold bears structural and functional significance

2020 ◽  
Vol 295 (43) ◽  
pp. 14653-14665
Author(s):  
Shashank Ranjan Srivastava ◽  
Radhakrishnan Mahalakshmi
Keyword(s):  
Functional Significance ◽  
Anion Channel ◽  
Dependent Manner ◽  
Structural Adaptation ◽  
Voltage Dependent Anion Channel ◽  
Voltage Dependent ◽  
Gated Channel ◽  
Engineered Structures ◽  
Transmembrane Transporters

Transmembrane β-barrels of eukaryotic outer mitochondrial membranes (OMMs) are major channels of communication between the cytosol and mitochondria and are indispensable for cellular homeostasis. A structurally intriguing exception to all known transmembrane β-barrels is the unique odd-stranded, i.e. 19-stranded, structures found solely in the OMM. The molecular origins of this 19-stranded structure and its associated functional significance are unclear. In humans, the most abundant OMM transporter is the voltage-dependent anion channel. Here, using the human voltage-dependent anion channel as our template scaffold, we designed and engineered odd- and even-stranded structures of smaller (V216, V217, V218) and larger (V220, V221) barrel diameters. Determination of the structure, dynamics, and energetics of these engineered structures in bilayer membranes reveals that the 19-stranded barrel surprisingly holds modest to low stability in a lipid-dependent manner. However, we demonstrate that this structurally metastable protein possesses superior voltage-gated channel regulation, efficient mitochondrial targeting, and in vivo cell survival, with lipid-modulated stability, all of which supersede the occurrence of a metastable 19-stranded scaffold. We propose that the unique structural adaptation of these transmembrane transporters exclusively in mitochondria bears strong evolutionary basis and is functionally significant for homeostasis.

scholarly journals VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease

Science ◽  
2019 ◽  
Vol 366 (6472) ◽  
pp. 1531-1536 ◽  
Author(s):  
Jeonghan Kim ◽  
Rajeev Gupta ◽  
Luz P. Blanco ◽  
Shutong Yang ◽  
Anna Shteinfer-Kuzmine ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Lupus Erythematosus ◽  
Anion Channel ◽  
Live Cells ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
Mitochondrial Outer Membrane Permeabilization ◽  
Extracellular Traps ◽  
Voltage Dependent ◽  
Positively Charged

Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering the type Ι interferon (IFN) response. Mitochondrial outer membrane permeabilization, which is required for mtDNA release, has been extensively studied in apoptotic cells, but little is known about its role in live cells. We found that oxidatively stressed mitochondria release short mtDNA fragments via pores formed by the voltage-dependent anion channel (VDAC) oligomers in the mitochondrial outer membrane. Furthermore, the positively charged residues in the N-terminal domain of VDAC1 interact with mtDNA, promoting VDAC1 oligomerization. The VDAC oligomerization inhibitor VBIT-4 decreases mtDNA release, IFN signaling, neutrophil extracellular traps, and disease severity in a mouse model of systemic lupus erythematosus. Thus, inhibiting VDAC oligomerization is a potential therapeutic approach for diseases associated with mtDNA release.

Abstract 5420: Dephosphorylation of the Cardiac Mitochondrial Voltage-Dependent Anion Channel Prevents Inhibition by Hexokinase

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Qunli Cheng ◽  
Zeljko J Bosnjak ◽  
Wai-Meng Kwok
Keyword(s):  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Adenine Nucleotide ◽  
Standard Procedure ◽  
Anion Channel ◽  
Mitochondrial Outer Membrane ◽  
Cyclophilin D ◽  
Voltage Dependent Anion Channel ◽  
Voltage Dependent ◽  
The Mean

The mitochondrial permeability transition pore (mPTP) has been implicated as the end effector in ischemic and pharmacological preconditioning. Though the molecular composition of the mPTP is thought to consist of cyclophilin D located in the mitochondrial matrix, adenine nucleotide translocase on the inner mitochondrial membrane, and the voltage-dependent anion channel (VDAC) on the outer mitochondrial membrane, recent studies have raised the possibility that VDAC may be a regulatory, rather than a major, component of mPTP. Nevertheless, VDAC is likely to be a critical component of the preconditioning signaling pathway since it is the main conduit for metabolite diffusion across the mitochondrial outer membrane. Yet, the direct measurements of cardiac VDAC activity and modulation have been limited. In the present study, we purified VDAC from rat hearts using standard procedure and investigated its modulation by phosphatase and hexokinase. VDAC was incorporated into planar lipid bilayer for measurements of channel activities. The channel exhibited the reported voltage-dependent gating. Several conductance states were identified, with the most prevalent between 1.5 to 2 nS in 0.5 M NaCl. Koenig’s polyanion, a VDAC blocker, triggered channel flickering and decreased the mean current by 78±6%. In the presence of phosphatase (1 unit/ml), the mean conductance significantly increased from 1.81±0.03 to 3.68±0.61 nS (n=9; mean±SEM). However, the addition of a recombinant hexokinase (5 units/ml; GenWay Biotech) had no significant effect on the phosphatase-enhanced VDAC current (n=4). In contrast, recombinant hexokinase alone significantly decreased the mean conductance from 1.75±0.05 to 0.79±0.19 nS (n=4). The addition of phosphatase reversed the inhibitory effect of hexokinase and further enhanced VDAC activity, increasing the mean conductance to 2.69±0.19 nS (n=4). Our results suggest that the dephosphorylation of VDAC prevents the inhibitory effects of hexokinase. Furthermore, VDAC activity suppressed by hexokinase can be reversed by dephosphorylation of the channel. In conclusion, we have reported on a novel observation at the functional level that basal phosphorylation of the cardiac VDAC may be required for its modulation by hexokinase.

scholarly journals In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death

2004 ◽  
Vol 377 (2) ◽  
pp. 347-355 ◽  
Author(s):  
Heftsi AZOULAY-ZOHAR ◽  
Adrian ISRAELSON ◽  
Salah ABU-HAMAD ◽  
Varda SHOSHAN-BARMATZ
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Direct Interaction ◽  
Anion Channel ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
Metabolic Intermediate ◽  
Voltage Dependent

In tumour cells, elevated levels of mitochondria-bound isoforms of hexokinase (HK-I and HK-II) result in the evasion of apoptosis, thereby allowing the cells to continue proliferating. The molecular mechanisms by which bound HK promotes cell survival are not yet fully understood. Our studies relying on the purified mitochondrial outer membrane protein VDAC (voltage-dependent anion channel), isolated mitochondria or cells in culture suggested that the anti-apoptotic activity of HK-I occurs via modulation of the mitochondrial phase of apoptosis. In the present paper, a direct interaction of HK-I with bilayer-reconstituted purified VDAC, inducing channel closure, is demonstrated for the first time. Moreover, HK-I prevented the Ca2+-dependent opening of the mitochondrial PTP (permeability transition pore) and release of the pro-apoptotic protein cytochrome c. The effects of HK-I on VDAC activity and PTP opening were prevented by the HK reaction product glucose 6-phosphate, a metabolic intermediate in most biosynthetic pathways. Furthermore, glucose 6-phosphate re-opened both the VDAC and the PTP closed by HK-I. The HK-I-mediated effects on VDAC and PTP were not observed using either yeast HK or HK-I lacking the N-terminal hydrophobic peptide responsible for binding to mitochondria, or in the presence of an antibody specific for the N-terminus of HK-I. Finally, HK-I overexpression in leukaemia-derived U-937 or vascular smooth muscle cells protected against staurosporine-induced apoptosis, with a decrease of up to 70% in cell death. These results offer insight into the mechanisms by which bound HK promotes tumour cell survival, and suggests that its overexpression not only ensures supplies of energy and phosphometabolites, but also reflects an anti-apoptotic defence mechanism.

scholarly journals Functions of BCL-XLat the Interface between Cell Death and Metabolism

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Judith Michels ◽  
Oliver Kepp ◽  
Laura Senovilla ◽  
Delphine Lissa ◽  
Maria Castedo ◽  
...  
Keyword(s):  
Cell Death ◽  
Mitochondrial Permeability Transition ◽  
Atp Synthesis ◽  
Anion Channel ◽  
Permeability Transition ◽  
Short Review ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
Regulated Necrosis ◽  
Voltage Dependent

The BCL-2 homolog BCL-XL, one of the two protein products ofBCL2L1, has originally been characterized for its prominent prosurvival functions. Similar to BCL-2, BCL-XLbinds to its multidomain proapoptotic counterparts BAX and BAK, hence preventing the formation of lethal pores in the mitochondrial outer membrane, as well as to multiple BH3-only proteins, thus interrupting apical proapoptotic signals. In addition, BCL-XLhas been suggested to exert cytoprotective functions by sequestering a cytosolic pool of the pro-apoptotic transcription factor p53 and by binding to the voltage-dependent anion channel 1 (VDAC1), thereby inhibiting the so-called mitochondrial permeability transition (MPT). Thus, BCL-XLappears to play a prominent role in the regulation of multiple distinct types of cell death, including apoptosis and regulated necrosis. More recently, great attention has been given to the cell death-unrelated functions of BCL-2-like proteins. In particular, BCL-XLhas been shown to modulate a number of pathophysiological processes, including—but not limited to—mitochondrial ATP synthesis, protein acetylation, autophagy and mitosis. In this short review article, we will discuss the functions of BCL-XLat the interface between cell death and metabolism.

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