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ATP transport through a single mitochondrial channel, VDAC, studied by current fluctuation analysis

T K Rostovtseva1, S M Bezrukov

  • 1Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

Biophysical Journal
|May 20, 1998
PubMed
Summary

Researchers used a "molecular Coulter counter" to study adenosine triphosphate (ATP) transport through the voltage-dependent anion channel (VDAC). They found ATP is attracted to the VDAC pore, influencing channel conductance and enabling diffusion coefficient calculation.

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Ion Channel Physiology

Background:

  • Mitochondrial ion channels, particularly the voltage-dependent anion channel (VDAC), play crucial roles in cellular energy metabolism.
  • Adenosine triphosphate (ATP) is the primary energy currency of the cell, and its transport across mitochondrial membranes is tightly regulated.

Purpose of the Study:

  • To investigate the transport of ATP molecules through a single VDAC channel using a "molecular Coulter counter" approach.
  • To quantify the interaction between ATP and the VDAC pore and determine the diffusion coefficient of ATP within the pore.

Main Methods:

  • Reconstitution of a single VDAC channel into a planar lipid bilayer.
  • Measurement of ATP-induced current fluctuations and changes in average ionic current.

Related Experiment Videos

  • Analysis of excess noise spectra to determine ATP diffusion characteristics.

    • Main Results:

    • ATP addition reduced both solution and channel conductance, with a stronger effect on the channel exhibiting saturation behavior.
    • Pronounced attraction of ATP molecules to the VDAC aqueous pore was observed.
    • The calculated diffusion coefficient of ATP within the VDAC pore (1.6-3.3 x 10^-11 m²/s) was one order of magnitude lower than in bulk solution.

    Conclusions:

    • The VDAC channel exhibits a significant affinity for ATP molecules.
    • The study provides a method to evaluate the effect of single ATP molecules on channel conductance.
    • The findings offer insights into ATP transport mechanisms at the mitochondrial level and align with previous flux measurements.