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Evidence for extra-mitochondrial localization of the VDAC/porin channel in eucaryotic cells
1Max-Planck-Institut für Experimentelle Medizin, Abteilung Immunchemie, Göttingen, Germany.
Abstract:
The expression of bacterial porin in outer membranes of gram-negative bacteria and of mitochondrial porin or voltage-dependent anion channel (VDAC) in outer mitochondrial membranes (OMM) of eucaryotic cells was demonstrated about 15 years ago. However, the expression of VDAC in the plasmalemma (PLM) of transformed human B lymphoblasts has recently been indicated by cytotoxicity and indirect immunofluorescence studies. New data suggest that the expression of VDAC may be even more widespread. Different cell types express porin channels in their PLM and in intracellular membranes other than OMM. The functional expression of these channels may differ in the various compartments since recent experiments have demonstrated that the voltage dependence and ion selectivity of mitochondrial VDAC may be altered by their interaction with modulators. The present paper proposes a unifying concept for the ion-selective channels of cell membranes, in particular, those whose regulation is affected in cystic fibrosis.
Insights
Voltage-dependent anion channels (VDAC) are found in more cell membranes than previously thought, including the plasmalemma. Their function may vary across cell compartments and be influenced by modulators, offering insights into cystic fibrosis.
Area of Science:
- Cell Biology
- Biophysics
- Molecular Medicine
Background:
- Bacterial porins and mitochondrial VDAC (voltage-dependent anion channel) in outer mitochondrial membranes (OMM) are well-established.
- Recent studies suggest VDAC expression extends to the plasmalemma (PLM) of human B lymphoblasts.
Purpose of the Study:
- To explore the widespread expression of VDAC in various cellular membranes beyond the OMM.
- To propose a unifying concept for ion-selective channels in cell membranes, particularly concerning cystic fibrosis.
Main Methods:
- Cytotoxicity assays.
- Indirect immunofluorescence studies.
- Analysis of VDAC channel properties (voltage dependence, ion selectivity) in different cellular compartments.
Main Results:
- Evidence indicates VDAC expression in the plasmalemma of transformed human B lymphoblasts.
- VDAC channels are expressed in cellular membranes other than OMM.
- Functional properties of VDAC channels can be modulated by interactions.
Conclusions:
- VDAC expression is more pervasive across cell types and membranes than previously recognized.
- Modulation of VDAC function by various factors impacts channel properties.
- Understanding these channels may provide insights into diseases like cystic fibrosis.