Assessing the role of residue E73 and lipid headgroup charge in VDAC1 voltage gating.
Beta-barrel channel gating
Cholesterol
Mitochondrial outer membrane
Phospholipids
Point mutations
Voltage-dependent anion channel
Journal
Biochimica et biophysica acta. Bioenergetics
ISSN: 1879-2650
Titre abrégé: Biochim Biophys Acta Bioenerg
Pays: Netherlands
ID NLM: 101731706
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
18
06
2018
revised:
05
10
2018
accepted:
04
11
2018
pubmed:
10
11
2018
medline:
2
8
2019
entrez:
10
11
2018
Statut:
ppublish
Résumé
The voltage-dependent anion channel (VDAC) is the most abundant protein of the mitochondrial outer membrane (MOM) where it regulates transport of ions and metabolites in and out of the organelle. VDAC function is extensively studied in a lipid bilayer system that allows conductance monitoring of reconstituted channels under applied voltage. The process of switching from a high-conductance state, open to metabolites, to a variety of low-conducting states, which excludes metabolite transport, is termed voltage gating and the mechanism remains poorly understood. Recent studies have implicated the involvement of the membrane-solvated residue E73 in the gating process through β-barrel destabilization. However, there has been no direct experimental evidence of E73 involvement in VDAC1 voltage gating. Here, using electrophysiology measurements, we exclude the involvement of E73 in murine VDAC1 (mVDAC1) voltage gating process. With an established protocol of assessing voltage gating of VDACs reconstituted into planar lipid membranes, we definitively show that mVDAC1 gating properties do not change when E73 is replaced by either a glutamine or an alanine. We further demonstrate that cholesterol has no effect on mVDAC1 gating characteristics, though it was shown that E73 is coordinating residue in the cholesterol binding site. In contrast, we found a pronounced gating effect based on the charge of the phospholipid headgroup, where the positive charge stimulates and negative charge suppresses gating. These findings call for critical evaluation of the existing models of VDAC gating and contribute to our understanding of VDAC's role in control of MOM permeability and regulation of mitochondrial respiration and metabolism.
Identifiants
pubmed: 30412693
pii: S0005-2728(18)30164-6
doi: 10.1016/j.bbabio.2018.11.001
pmc: PMC8283775
mid: NIHMS1718229
pii:
doi:
Substances chimiques
Membrane Lipids
0
Vdac1 protein, mouse
0
Glutamic Acid
3KX376GY7L
Voltage-Dependent Anion Channel 1
EC 1.6.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
22-29Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM078844
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124783
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA HD000072
Pays : United States
Informations de copyright
Copyright © 2018. Published by Elsevier B.V.
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