Renaissance of VDAC: New Insights on a Protein Family at the Interface between Mitochondria and Cytosol

Pinto, Vito De

doi:10.3390/biom11010107

Cited by 46 publications

(40 citation statements)

References 90 publications

(136 reference statements)

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“…In this perspective, VDACs are widely considered essential for the maintenance of the mitochondrial bioenergetic and the communication between the organelle and the rest of the cell (as reviewed in Shoshan-Barmatz et al, 2010 ; De Pinto, 2021 ).…”

Section: The Structure and Functions Of Vdac Proteinsmentioning

confidence: 99%

Voltage-Dependent Anion Selective Channel Isoforms in Yeast: Expression, Structure, and Functions

et al. 2021

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Mitochondrial porins, also known as voltage-dependent anion selective channels (VDACs), are pore-forming molecules of the outer mitochondrial membranes, involved in the regulation of metabolic flux between cytosol and mitochondria. Playing such an essential role, VDAC proteins are evolutionary conserved and isoforms are present in numerous species. The quest for specific function(s) related to the raise of multiple isoforms is an intriguing theme. The yeast Saccharomyces cerevisiae genome is endowed with two different VDAC genes encoding for two distinct porin isoforms, definitely less characterized in comparison to mammalian counterpart. While yVDAC1 has been extensively studied, the second isoform, yVDAC2, is much less expressed, and has a still misunderstood function. This review will recapitulate the known and poorly known information in the literature, in the light of the growing interest about the features of VDAC isoforms in the cell.

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Section: The Structure and Functions Of Vdac Proteinsmentioning

confidence: 99%

Voltage-Dependent Anion Selective Channel Isoforms in Yeast: Expression, Structure, and Functions

et al. 2021

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“…Mitochondrial outer membranes contain large amounts of the mitochondrial porin termed the voltage-dependent anion channel (VDAC) [92,93]. When reconstituted into the artificial lipid bilayers, it forms ion channels that are phenotypically reminiscent of the maxi-anion channels: they have large conductance of app.…”

Section: Molecular Identity Of Maxi-cl: Rejected Candidatesmentioning

confidence: 99%

The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

Sabirov

Islam

Okada

et al. 2021

Life

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The Maxi-Cl phenotype accounts for the majority (app. 60%) of reports on the large-conductance maxi-anion channels (MACs) and has been detected in almost every type of cell, including placenta, endothelium, lymphocyte, cardiac myocyte, neuron, and glial cells, and in cells originating from humans to frogs. A unitary conductance of 300–400 pS, linear current-to-voltage relationship, relatively high anion-to-cation selectivity, bell-shaped voltage dependency, and sensitivity to extracellular gadolinium are biophysical and pharmacological hallmarks of the Maxi-Cl channel. Its identification as a complex with SLCO2A1 as a core pore-forming component and two auxiliary regulatory proteins, annexin A2 and S100A10 (p11), explains the activation mechanism as Tyr23 dephosphorylation at ANXA2 in parallel with calcium binding at S100A10. In the resting state, SLCO2A1 functions as a prostaglandin transporter whereas upon activation it turns to an anion channel. As an efficient pathway for chloride, Maxi-Cl is implicated in a number of physiologically and pathophysiologically important processes, such as cell volume regulation, fluid secretion, apoptosis, and charge transfer. Maxi-Cl is permeable for ATP and other small signaling molecules serving as an electrogenic pathway in cell-to-cell signal transduction. Mutations at the SLCO2A1 gene cause inherited bone and gut pathologies and malignancies, signifying the Maxi-Cl channel as a perspective pharmacological target.

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“…It is well known that the universal pathway for metabolite transport across the outer mitochondrial membrane is formed by the VDAC, which may be formed by different VDAC paralogs (e.g., [ 126 , 127 , 128 , 129 , 130 ]). The molecular mass cut-off for the transported molecules is assumed to be about 4 kDa although the limit could be decreased when VDAC switches to lower conducting substates featuring less anion selectivity [ 131 ].…”

Section: Non-proteinaceous Molecules Transported By Protein Import Channelsmentioning

confidence: 99%

“…Moreover, it has been observed that blocking the TOM complex with an imported protein decreased superoxide anion (O 2 •− ) release from mitochondria, particularly in the absence of functional yVDAC1 [ 135 ]. Notably, yeast mitochondria contain two VDAC paralogs (i.e., yVDAC1 and yVDAC2 [ 136 , 137 ]), both of which can form channels of comparable electrophysiological characteristics [ 130 ], but differ in their expression levels and (likely) substrate selectivity [ 138 ]. These postulated differences coincide with a yVDAC2 contribution to the global permeability of the mitochondrial outer membrane that has remained undetected to date [ 4 , 139 ].…”

Section: Non-proteinaceous Molecules Transported By Protein Import Channelsmentioning

confidence: 99%

The Diversity of the Mitochondrial Outer Membrane Protein Import Channels: Emerging Targets for Modulation

2021

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The functioning of mitochondria and their biogenesis are largely based on the proper function of the mitochondrial outer membrane channels, which selectively recognise and import proteins but also transport a wide range of other molecules, including metabolites, inorganic ions and nucleic acids. To date, nine channels have been identified in the mitochondrial outer membrane of which at least half represent the mitochondrial protein import apparatus. When compared to the mitochondrial inner membrane, the presented channels are mostly constitutively open and consequently may participate in transport of different molecules and contribute to relevant changes in the outer membrane permeability based on the channel conductance. In this review, we focus on the channel structure, properties and transported molecules as well as aspects important to their modulation. This information could be used for future studies of the cellular processes mediated by these channels, mitochondrial functioning and therapies for mitochondria-linked diseases.

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Renaissance of VDAC: New Insights on a Protein Family at the Interface between Mitochondria and Cytosol

Cited by 46 publications

References 90 publications

Voltage-Dependent Anion Selective Channel Isoforms in Yeast: Expression, Structure, and Functions

Voltage-Dependent Anion Selective Channel Isoforms in Yeast: Expression, Structure, and Functions

The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

The Diversity of the Mitochondrial Outer Membrane Protein Import Channels: Emerging Targets for Modulation

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