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Journal Articles Biophysical Journal Year : 2023

VDAC interactions with lipids and their effect on isoform specificity

Abstract

The Voltage-Dependent Anion Channel (VDAC) is a β-barrel, the most abundant protein of the mitochondrial outer membrane, allowing passage of ions and metabolites (such as ATP, ADP, NADH⋯) in and out of the mitochondria. Besides its transport function, VDAC is also implicated in mitochondrial regulation with roles in apoptosis, calcium homeostasis or neurodegeneration. However, its role in those different pathways remains to be understood at the molecular level. VDAC possesses 3 isoforms in mammals (VDAC1, 2 and 3), sharing a high sequence identity, the same architecture and an overlapping tissue distribution. They display very similar transport properties such as conductance, selectivity and voltage-induced closure while their isoform specificity originates from their different interaction with partner proteins. This may determine their unique role in mitochondrial regulation, where each isoform seems to have different functions and a different set of partners: VDAC1 is implicated in neurodegeneration (Alzheimer and Parkinson disease), VDAC2 in apoptosis and calcium homeostasis, and VDAC3 probably in spermatogenesis and oxidative stress. Using a combination of biochemistry, molecular dynamics and electrophysiology, we investigated the lipid organization around each VDAC isoform and their impact on VDAC function. Our data suggest that the three isoforms have different affinities for lipids, and that could contribute to the selection of interacting partners.

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Biophysics
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Dates and versions

hal-04429164 , version 1 (31-01-2024)

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Jean-Pierre Duneau, Maria Queralt-Martin, Lucie Bergdoll. VDAC interactions with lipids and their effect on isoform specificity. Biophysical Journal, 2023, 122 (3), pp.373a. ⟨10.1016/j.bpj.2022.11.2056⟩. ⟨hal-04429164⟩
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