Conformational plasticity of mitochondrial VDAC2 controls the kinetics of its interaction with cytosolic proteins.

ABSTRACT: The voltage-dependent anion channel (VDAC) is a key conduit of the mitochondrial outer membrane for water-soluble metabolites and ions. Among the three mammalian isoforms, VDAC2 is unique because of its embryonic lethality upon knockout. Using single-molecule electrophysiology, we investigate the biophysical properties that distinguish VDAC2 from VDAC1 and VDAC3. Unlike the latter, VDAC2 exhibits dynamic switching between multiple high-conductance, anion-selective substates. Using α-synuclein (αSyn)-a known VDAC1 cytosolic regulator-we found that higher-conductance substates correlate with increased on-rates of αSyn-VDAC2 interaction but shorter blockage times, maintaining a consistent equilibrium constant across all substates. This suggests that αSyn detects VDAC2's dynamic structural var

SUBMITTER: Rosencrans WM 

PROVIDER: S-EPMC12017312 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature