VDAC, a multi-functional mitochondrial protein regulating cell life and death

Shoshan‐Barmatz, Varda; Pinto, Vito De; Zweckstetter, Markus; Raviv, Ziv; Keinan, Nurit; Arbel, Nir

doi:10.1016/j.mam.2010.03.002

Cited by 644 publications

(763 citation statements)

References 599 publications

(915 reference statements)

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“…Thus, the mRNA profiles in mature spermatozoa should be roughly similar to mRNAs in the testis and can reflect the transcription and translation of genes during spermatogenesis [25]. Human three VDAC genes, being located on autosomes, are not previously considered a kind of male infertility genes [31,32]. Some recent studies had reported that VDAC protein was expressed at testicular level, incorpo- rated into mature spermatozoa, and was implicated in sperm motility.…”

Section: Discussionmentioning

confidence: 98%

Analysis and difference of voltage-dependent anion channel mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia

Liu

Wang

et al. 2010

J Assist Reprod Genet

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Purpose To analyze the abundance and difference of voltagedependent anion channel (VDAC) mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia. Methods High motile and low motile spermatozoa were separated respectively from ejaculates of 36 donors and 40 patients using a discontinuous Percoll gradient centrifugation. Real-Time PCR was performed to detect mRNA abundance and difference of three VDAC subtypes between two groups with different sperm motility.Results Real-Time PCR demonstrated that three VDAC mRNAs were present in mature spermatozoa. The VDAC2 mRNA level in ejaculated spermatozoa of patients was significantly higher than that of donors. No significant differences of VDAC1 and VDAC3 mRNA levels were found between two groups. Conclusion The high abundance of VDAC2 mRNA seemed to have a positive correlation with low sperm motility. The abnormal expression of VDAC might be related to male infertility with idiopathic asthenozoospermia.

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Section: Discussionmentioning

confidence: 98%

Analysis and difference of voltage-dependent anion channel mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia

Liu

Wang

et al. 2010

J Assist Reprod Genet

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“…VDAC1 is a promiscuous ion channel, also known as mitochondrial porin, and is most often located on the outer membrane of mitochondria, although has also been reported to be present on cell plasma membranes [112]. VDAC1 plays a complex and important role in a variety of cell functions such as ATP rationing, Ca 2+ homeostasis, apoptosis, and protection against oxidative stress.…”

Section: Vdac1 (Mitochondrial Porin)mentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

446

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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“…1 It is the most abundant protein in the mitochondrial outer membrane and governs the transport of metabolites, e.g. ATP, ADP, and glutamate, between the cytosol and the mitochondrion.…”

Section: Introductionmentioning

confidence: 99%

Voltage-dependent structural changes of the membrane-bound anion channel hVDAC1 probed by SEIRA and electrochemical impedance spectroscopy

Kozuch

Weichbrodt

Millo

et al. 2014

Phys. Chem. Chem. Phys.

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The voltage-dependent anion channel (VDAC) is a transmembrane protein that regulates the transfer of metabolites between the cytosol and the mitochondrium. Opening and partial closing of the channel is known to be driven by the transmembrane potential via a mechanism that is not fully understood. In this work, we employed a spectroelectrochemical approach to probe the voltage-induced molecular structure changes of human VDAC1 (hVDAC1) embedded in a tethered bilayer lipid membrane on a nanostructured Au electrode. The model membrane consisted of a mixed self-assembled monolayer of 6-mercaptohexanol and (cholesterylpolyethylenoxy)thiol, followed by the deposition of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine vesicles including hVDAC1. The stepwise assembly of the model membrane and the incorporation of hVDAC1 were monitored by surface enhanced infrared absorption and electrochemical impedance spectroscopy. Difference spectra allowed for identifying the spectral changes which may be associated with the transition from the open to the ''closed'' states by shifting the potential above or below the transmembrane potential determined to be ca. 0.0 V vs. the open circuit potential. These spectral changes were interpreted on the basis of the orientation-and distancedependent IR enhancement and indicate alterations of the inclination angle of the b-strands as crucial molecular events, reflecting an expansion or contraction of the b-barrel pore. These protein structural changes that do not confirm nor exclude the reorientation of the a-helix are either directly induced by the electric field or a consequence of a potential-dependent repulsion or attraction of the bilayer.

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VDAC, a multi-functional mitochondrial protein regulating cell life and death

Cited by 644 publications

References 599 publications

Analysis and difference of voltage-dependent anion channel mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia

Analysis and difference of voltage-dependent anion channel mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia

Molecular Targets of Cannabidiol in Neurological Disorders

Voltage-dependent structural changes of the membrane-bound anion channel hVDAC1 probed by SEIRA and electrochemical impedance spectroscopy

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