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Updated: Oct 14, 2025

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Extracellular Signal-Regulated Kinase1 (ERK1)-Mediated Phosphorylation of Voltage-Dependent Anion Channel (VDAC)

Chetan Malik1, Shumaila Iqbal Siddiqui1, Subhendu Ghosh2

  • 1Department of Biophysics, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India.

The Journal of Membrane Biology
|November 3, 2021
PubMed

Insights

Extracellular signal-regulated kinase 1 (ERK1) phosphorylates voltage-dependent anion channel (VDAC), inhibiting its function. This VDAC phosphorylation by ERK1 leads to channel closure, impacting mitochondrial function.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Physiology

Background:

  • Mitogen-activated protein kinases, such as ERK1, regulate critical cellular processes.
  • Voltage-dependent anion channel (VDAC) is a key protein in the outer mitochondrial membrane, controlling metabolite transport.

Purpose of the Study:

  • To investigate the interaction between ERK1 and VDAC.
  • To determine the functional consequences of ERK1-mediated VDAC phosphorylation.

Main Methods:

  • In vitro electrophysiology using artificial planar lipid bilayers to study VDAC single-channel currents.
  • Biochemical assays including Pro-Q diamond dye staining and mass spectrometry to confirm and map VDAC phosphorylation.
  • Treatment with alkaline phosphatase to assess dephosphorylation effects.

Main Results:

  • ERK1 directly phosphorylates VDAC in the presence of Mg2+-ATP.
  • VDAC phosphorylation by ERK1 inhibits its single-channel currents on artificial membranes.
  • Dephosphorylation by alkaline phosphatase partially restores VDAC channel activity.
  • Mass spectrometry identified phosphorylation sites at Threonine 33, Threonine 55, and Serine 35 on VDAC.
  • Phosphorylation results in VDAC channel closure.

Conclusions:

  • ERK1-mediated phosphorylation of VDAC leads to its functional inhibition.
  • Phosphorylation of VDAC by ERK1 closes the channel, suggesting a regulatory mechanism for mitochondrial function.
Keywords:
ApoptosisBilayer electrophysiologyExtracellular signal-regulated kinasePhosphorylationVoltage-dependent anion channel

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