To my knowledge there are only a few reports on autoantibody reactivity against VDAC concerning different syndromes, however, worth to mention in the context of the study under consideration [1-4].

The paper of Gonzalez-Gronow et al. (2010), referring on antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase-I in children with autism [4], appears to be of special interest.

Accordingly autistic children show elevated serum levels of autoantibodies to several proteins essential for the function of normal brains. Furthermore, type-1 voltage-dependent anion channel (VDAC-1) and hexokinase-I were identified as targets of this autoimmunity in autistic children. These autoantibodies were purified using immuno affinity chromatographic techniques.

Both antibodies induce apoptosis of cultured human neuroblastoma cells.

In contrast, antibodies directed against the N-terminal helical stretch of type-1 VDAC have been shown to block apoptosis.

To note, the anti-VDAC antibody observed by Gonzalez-Gronow´s laboratory recognizes its epitope between Lys 235 and Lys 355 of the channel molecule; the blocking Abs under discussion here find their epitope(s) inside the acetylated N-terminal stretch of type-1 VDAC up to position eleven.

Type-1 VDAC has been found in the cell membrane of different cell types, i.e. neuronal, non neuronal, red blood cells [5].

Concerning function, the channel is involved in cell volume regulation and thus in apoptosis [5].

However, corresponding antibodies have been shown to block the apoptotic volume decrease (AVD) of neuronal cells stimulated by staurosporine or amyloid Aß peptides, respectively [6,7]

Conclusion
A synopsis of these date may help to better understand the involvement of type-1 VDAC in the pathogenesis of autism, Alzheimer Disease [8,9] and other syndromes [1-3].


References:
[1] Ning L, Pan B, Zhao YP, Liao Q, Zhang TP, Chen G, Wang WB, Yang YC.[Immuno-proteomic screening of human pancreatic cancer associated membrane antigens for early diagnosis]. [Article in Chinese] Zhonghua Wai Ke Za Zhi. 2007 Jan 1;45(1):34-8.

[2] Wang WB, Zhao YP, Ning L, Liao Q, Wu YD.[Research of immunogenic membrane antigens of pancreatic cancer]. [Article in Chinese] Zhonghua Wai Ke Za Zhi. 2009 Jul 1;47(13):1006-9.

[3] Kikuchi T, Yoshida Y, Morioka T, Gejyo F, Oite T.Human voltage-dependent anion selective channel 1 is a target antigen for antiglomerular endothelial cell antibody in mixed connective tissue disease. Mod Rheumatol. 2008; 18(6):570-7.

[4] Gonzalez-Gronow M, Cuchacovich M, Francos R, Cuchacovich S, Fernandez Mdel P, Blanco A, Bowers EV, Kaczowka S, Pizzo SV. Antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase-I in children with autism. J Neuroimmunol. 2010 Oct 8;227(1-2):153-61.

[5] Thinnes FP. New findings concerning vertebrate porin II--on the relevance of glycine motifs of type-1 VDAC. Mol Genet Metab. 2013 Apr;108(4):212-24.

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

[7] Marin R, Ramírez CM, González M, González-Muñoz E, Zorzano A, Camps M, Alonso R, Díaz M. Voltage-dependent anion channel (VDAC) participates in amyloid beta-induced toxicity and interacts with plasma membrane estrogen receptor alpha in septal and hippocampal neurons. Mol Membr Biol. 2007 Mar-Apr;24(2):148-60.

[8] Thinnes FP. Amyloid Aß , cut from APP by ß-secretase BACE1 and γ-secretase, induces apoptosis via opening type-1 porin/VDAC in cell membranes of hypometabolic cells-A basic model for the induction of apoptosis!? Mol Genet Metab. 2010 Oct-Nov;101(2-3):301-3.

[9] Thinnes FP. Apoptogenic interactions of plasmalemmal type-1 VDAC and Aβ peptides via GxxxG motifs induce Alzheimer's disease - a basic model of apoptosis? Wien Med Wochenschr. 2011 May;161(9-10):274-6.