Assessing the role of residue E73 and lipid headgroup charge in VDAC1 voltage gating

Queralt-Martín, María; Bergdoll, Lucie; Jacobs, Daniel; Bezrukov, Sergey M.; Abramson, Jeff; Rostovtseva, Tatiana K.

doi:10.1016/j.bbabio.2018.11.001

Cited by 33 publications

(65 citation statements)

References 60 publications

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“…However, mVDAC3 had the highest number of insertions and was selected for additional gating studies. In these experiments, PLM were composed of soybean PLE with 5% cholesterol, as this mixture promotes gating at lower voltages than PLM composed of DOPC/DOPE/2DOPG membranes (Queralt-Martín et al, 2019). Both mVDAC3 and mVDAC1 displayed similar current responses (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To maximize binding of α-syn and maintain the open state of VDAC, a PLM lipid composition of DOPC/DOPE/2DOPG was used, which virtually abolishes voltage gating at applied voltages <60 mV (Queralt-Martín et al, 2019). Furthermore, the higher content of anionic DOPG in the lipid mixture increases the on-rate of α-syn with VDAC (Jacobs et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

“…Voltage gating is another property of VDACs that is remarkably well conserved across different species and isoforms. The molecular mechanism of VDAC voltage gating remains poorly understood, and this is an active area of research (Mertins et al, 2012; Teijido et al, 2012; Zachariae et al, 2012; Rappaport et al, 2015; Queralt-Martín et al, 2019). Given the likely similarities in structure between VDAC1 and VDAC3 (Messina et al, 2012; Amodeo et al, 2014), a comparable gating behavior is expected for both channels.…”

Section: Discussionmentioning

confidence: 99%

“…VDAC ion selectivity was measured in 1 M (cis) versus 0.2 M KCl (trans) gradient, buffered with 5 mM HEPES at pH 7.4, as described previously (Teijido et al, 2014; see Supplemental methods). VDAC voltage-gating was measured on multichannel membranes using a previously described protocol (Colombini, 1989; Rostovtseva et al, 2006; Queralt-Martín et al, 2019; see Supplemental methods).…”

Section: Methodsmentioning

confidence: 99%

“…In total, we compiled data from recombinant human and mouse VDAC3 expressed in Escherichia coli and refolded in lauryldimethylamine oxide (LDAO) and recombinant human VDAC3 expressed in yeast and isolated from mitochondria. All samples were studied under the same conditions, which is imperative because electrophysiological properties are known to be sensitive to the concentration and type of salt (NaCl vs. KCl; Rostovtseva and Bezrukov, 1998, 2015), pH (Bowen et al, 1985; Colombini, 1989; Teijido et al, 2014), and membrane lipid composition (Rostovtseva et al, 2006; Mlayeh et al, 2017; Queralt-Martín et al, 2019). We show that all VDAC3 samples used in our study exhibit basic electrophysiological properties (open channel conductance, anion selectivity, and voltage gating) similar to VDAC1, indicating that VDAC3 can concurrently facilitate metabolite exchange.…”

Section: Introductionmentioning

confidence: 99%

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A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology

Queralt-Martín

Bergdoll

Teijido

et al. 2020

Journal of General Physiology

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Voltage-dependent anion channel (VDAC) is the major pathway for the transport of ions and metabolites across the mitochondrial outer membrane. Among the three known mammalian VDAC isoforms, VDAC3 is the least characterized, but unique functional roles have been proposed in cellular and animal models. Yet, a high-sequence similarity between VDAC1 and VDAC3 is indicative of a similar pore-forming structure. Here, we conclusively show that VDAC3 forms stable, highly conductive voltage-gated channels that, much like VDAC1, are weakly anion selective and facilitate metabolite exchange, but exhibit unique properties when interacting with the cytosolic proteins α-synuclein and tubulin. These two proteins are known to be potent regulators of VDAC1 and induce similar characteristic blockages (on the millisecond time scale) of VDAC3, but with 10- to 100-fold reduced on-rates and altered α-synuclein blocking times, indicative of an isoform-specific function. Through cysteine scanning mutagenesis, we found that VDAC3’s cysteine residues regulate its interaction with α-synuclein, demonstrating VDAC3-unique functional properties and further highlighting a general molecular mechanism for VDAC isoform-specific regulation of mitochondrial bioenergetics.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology

Queralt-Martín

Bergdoll

Teijido

et al. 2020

Journal of General Physiology

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Voltage‐activated complexation of α‐synuclein with three diverse β‐barrel channels: VDAC, MspA, and α‐hemolysin

et al. 2021

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Voltage-activated complexation is the process by which a transmembrane potential drives complex formation between a membrane-embedded channel and a soluble or membrane-peripheral target protein. Metabolite and calcium flux across the mitochondrial outer membrane was shown to be regulated by voltage-activated complexation of the voltage-dependent anion channel (VDAC) and either dimeric tubulin or αsynuclein (αSyn). However, the roles played by VDAC's characteristic attributes-its anion selectivity and voltage gating behavior-have remained unclear. Here, we compare in vitro measurements of voltage-activated complexation of αSyn with three wellcharacterized β-barrel channels-VDAC, MspA, and α-hemolysin-that differ widely in their organism of origin, structure, geometry, charge density distribution, and voltage gating behavior. The voltage dependences of the complexation dynamics for the different channels are observed to differ quantitatively but have similar qualitative features. In each case, energy landscape modeling describes the complexation dynamics in a manner consistent with the known properties of the individual channels, while voltage gating does not appear to play a role. The reaction free energy landscapes thus calculated reveal a non-trivial dependence of the αSyn/channel complex stability on the surface density of αSyn.

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Molecular mechanism of olesoxime-mediated neuroprotection through targeting α-synuclein interaction with mitochondrial VDAC

Rovini

Gurnev

Beilina

et al. 2019

Cell. Mol. Life Sci.

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Assessing the role of residue E73 and lipid headgroup charge in VDAC1 voltage gating

Cited by 33 publications

References 60 publications

A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology

A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology

Voltage‐activated complexation of α‐synuclein with three diverse β‐barrel channels: VDAC, MspA, and α‐hemolysin

Molecular mechanism of olesoxime-mediated neuroprotection through targeting α-synuclein interaction with mitochondrial VDAC

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