A soluble mitochondrial protein increases the voltage dependence of the mitochondrial channel, VDAC

M Y Liu1, M Colombini

  • 1Department of Zoology, University of Maryland, College Park 20742.

Insights

A newly discovered mitochondrial protein, the VDAC modulator, amplifies the voltage-dependent gating of the voltage-dependent anion channel (VDAC). This protein enhances VDAC channel sensitivity to cellular microenvironment changes, regulating metabolic flux.

Area of Science:

  • Mitochondrial biophysics
  • Molecular biology
  • Cellular physiology

Background:

  • The mitochondrial outer membrane channel, voltage-dependent anion channel (VDAC), plays a crucial role in regulating metabolite transport.
  • VDAC exhibits voltage-dependent gating properties, influencing cellular metabolism.
  • The precise molecular mechanisms modulating VDAC's voltage dependence are not fully understood.

Purpose of the Study:

  • To identify and characterize proteins that modulate the voltage-dependent properties of VDAC.
  • To investigate the functional consequences of VDAC modulation on channel gating and cellular metabolism.

Main Methods:

  • Isolation and purification of a soluble protein from mitochondria.
  • Electrophysiological recordings of VDAC channel activity in the presence of the isolated protein.
  • Analysis of VDAC channel gating kinetics and voltage dependence at varying protein concentrations.

Main Results:

  • A soluble mitochondrial protein, termed VDAC modulator, was identified and isolated.
  • The VDAC modulator significantly increased the voltage dependence of VDAC channels (2-3 fold) at concentrations of 20 µg/ml.
  • At higher concentrations (50-100 µg/ml), the modulator induced channel block or closure at low membrane potentials, while others showed enhanced voltage dependence.

Conclusions:

  • The VDAC modulator acts as an amplifier, increasing VDAC channel sensitivity to membrane potential changes.
  • This modulation provides a mechanism for fine-tuning metabolic flux across the outer mitochondrial membrane.
  • The VDAC modulator represents a novel regulatory factor controlling mitochondrial function and cellular energy homeostasis.

Related Concept Videos

The ADP/ATP Carrier Protein01:42

The ADP/ATP Carrier Protein

ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...