While the extra-mitochondrial incorporation of mammalian type-1 VDAC/porin into the plasma lemma is widely accepted the function of the channel in this cell compartment is still under debate (1-3); however the channel interacts with fluoxetine (4,5).

There are data data from different laboratories clearly documenting the channel´s involvement in cell volume regulation and, thus, apoptosis. However, the regulatory volume decrease (RVD) as well as the apoptotic volume decrease (AVD) after apoptotic stimulation of different cell types with staurosporin or amyloid Aß peptides, respectively, has been blocked by cell outside application of different anti-VDAC antibodies (6-10).

Concerning the context under discussion here it may be worth to point to a recent paper that reports on prostacyclin receptor-mediated ATP release from erythrocytes requiring type-1 VDAC (11). Taken together, plasma lemmal-integrated type-1 VDAC appears as a player in systemic regulatory processes.


References:

1) Voltage-dependent anion-selective channel (VDAC) in the plasma membrane.
De Pinto V, Messina A, Lane DJ, Lawen A.
FEBS Lett. 2010 May 3;584(9):1793-9. doi: 10.1016/j.febslet.2010.02.049. Epub 2010 Feb 23. Review.

2) Plasmalemmal VDAC controversies and maxi-anion channel puzzle.
Sabirov RZ, Merzlyak PG.
Biochim Biophys Acta. 2012 Jun;1818(6):1570-80. doi: 10.1016/j.bbamem.2011.09.024. Epub 2011 Oct 1.

3) On a fully closed state of native human type-1 VDAC enriched in Nonidet P40.
Thinnes FP, Burckhardt G.
Mol Genet Metab. 2012 Nov;107(3):632-3. doi: 10.1016/j.ymgme.2012.08.015. Epub 2012 Aug 29.

4) Does fluoxetine (Prozak) block mitochondrial permeability transition by blocking VDAC as part of permeability transition pores?
Thinnes FP.
Mol Genet Metab. 2005 Apr;84(4):378.

5) VDAC1: from structure to cancer therapy.
Shoshan-Barmatz V, Mizrachi D.
Front Oncol. 2012;2:164. doi: 10.3389/fonc.2012.00164. Epub 2012 Nov 29.



6) Studies on human porin XXII: cell membrane integrated human porin channels are involved in regulatory volume decrease (RVD) of HeLa cells.
Thinnes FP, Hellmann KP, Hellmann T, Merker R, Brockhaus-Pruchniewicz U, Schwarzer C, Walter G, Götz H, Hilschmann N.
Mol Genet Metab. 2000 Apr;69(4):331-7.

7) Voltage-dependent anion channel-1 (VDAC-1) contributes to ATP release and cell volume regulation in murine cells.
Okada SF, O'Neal WK, Huang P, Nicholas RA, Ostrowski LE, Craigen WJ, Lazarowski ER, Boucher RC.
J Gen Physiol. 2004 Nov;124(5):513-26. Epub 2004 Oct 11.

8) Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli.
Elinder F, Akanda N, Tofighi R, Shimizu S, Tsujimoto Y, Orrenius S, Ceccatelli S.
Cell Death Differ. 2005 Aug;12(8):1134-40.

9) Voltage-dependent anion channels (VDAC) in the plasma membrane play a critical role in apoptosis in differentiated hippocampal neurons but not in neural stem cells.
Akanda N, Tofighi R, Brask J, Tamm C, Elinder F, Ceccatelli S.
Cell Cycle. 2008 Oct;7(20):3225-34. Epub 2008 Oct 20.

10) Voltage-dependent anion channel as a resident protein of lipid rafts: post-transductional regulation by estrogens and involvement in neuronal preservation against Alzheimer's disease.
Herrera JL, Diaz M, Hernández-Fernaud JR, Salido E, Alonso R, Fernández C, Morales A, Marin R.
J Neurochem. 2011 Mar;116(5):820-7. doi: 10.1111/j.1471-4159.2010.06987.x. Epub 2011 Jan 7. Review.

11) Prostacyclin receptor-mediated ATP release from erythrocytes requires the voltage-dependent anion channel.
Sridharan M, Bowles EA, Richards JP, Krantic M, Davis KL, Dietrich KA, Stephenson AH, Ellsworth ML, Sprague RS.
Am J Physiol Heart Circ Physiol. 2012 Feb 1;302(3):H553-9. doi: 10.1152/ajpheart.00998.2011. Epub 2011 Dec 9.