Phosphorylation, nitrosation and plasminogen K3 modulation make VDAC-1 lucid as part of the extrinsic apoptotic pathway-Resulting thesis: Native VDAC-1 indispensible for finalisation of its 3D structure.

Native and recombinant VDAC preparations differ in their acetylation, phosphorylation and nitrosation state; additionally, proteineous modulators are missing in the latter. They thus vary in channel characteristics, as can be taken from comparative black lipid bilayer experiments. Furthermore, the multi-compartment expression makes expect even differing native VDAC-1 molecules.

Opening up of plasmalemma type-1 VDAC to form apoptotic "find me signal" pathways is essential in early apoptosis - evidence from the pathogenesis of cystic fibrosis resulting from failure of apoptotic cell clearance followed by sterile inflammation.

Cell membrane-standing type-1 VDAC is involved in cell volume regulation and thus apoptosis. The channel has been shown to figure as a pathway for osmolytes of varying classes, ATP included. An early event in apoptotic cell death is the release of "find me signals" by cells that enter the apoptotic process.

New findings concerning vertebrate porin II--on the relevance of glycine motifs of type-1 VDAC.

New findings concerning vertebrate porin part I was published in 1997, then summarizing early data and reflections regarding the molecular structure of vertebrate voltage-dependent anion-selective channels, VDAC/eukaryotic porin, and the extra-mitochondrial expression pattern of human type-1 VDAC. Meanwhile, endeavors of different laboratories confirmed and widened this beginning by encircling the function of the channels. Regarding the function of mitochondrial outer membrane-standing VDACs the channels are established parts of the intrinsic apoptotic pathway and thus therapeutic targets in studies on several diseases: cancer, Alzheimer's disease, Down Syndrome, Parkinson's disease, Amyotrophic Lateral Sclerosis, cystic fibrosis and malaria.

On a fully closed state of native human type-1 VDAC enriched in Nonidet P40.

There is indication that human type-1 VDAC/Porin31HL complexes, when purified from highly enriched cell membrane preparations of human B-lymphocytes by classical ion-exchange chromatography in the detergent Nonidet P40, rest in fully closed state, its N-terminus being accessible for mAbs. Cholesterol appears to be involved as a channel modulator. The channel switches to anion-selective or "open state" while being incorporated into black membranes at zero transmembrane potential.

Why cancer survivors have a lower risk of Alzheimer disease.

Tying up two recent lines of experimental evidence may help explain this vital issue. On the one hand, data indicate that cancerous transformations of cells include changes in expression level and/or the functionality of multidrug resistance modulators which then disturb chemotherapy. On the other hand, studies have shown that some of the ABC transporters--at the blood-brain barrier--work as effective efflux pumps for amyloid Aβ peptides.

To the knowledge of the 20GYGFG24 sequence stretch of type-1 VDAC: to understand why BCl-XL B4 domain peptides keep HeLa cells closed in hypotonic surroundings.

Type-1 VDAC/porin, as a part of its voltage sensor, includes a GxxxG motif sequence that has been shown to work as an ATP-binding site. The motif has also been demonstrated to function as an aggregation/membrane perturbation sequence that opens VDAC in the plasmalemma of neuronal cells in experiment on apoptosis induction. Here it is discussed how type-1 VDAC channels at the cell surface of HeLa cells in hypotonic surroundings might be kept closed after pre-incubation with BCl-XL B4 domain peptides.

Apoptogenic interactions of plasmalemmal type-1 VDAC and Aβ peptides via GxxxG motifs induce Alzheimer's disease - a basic model of apoptosis?

Human type-1 porin/VDAC (voltage-dependent anion channel) carries a GxxxG motif in its N-terminal part, traversing the β-barrel, while the Alzheimer's disease (AD) relevant amyloid peptides Aβ1-42 and Aβ1-40 show a series of corresponding motifs close to their C-terminus. GxxxG motifs are established as aggregation/membrane perturbation motifs. These peptide primary structure data support a proposal I recently made on the basis of a synopsis of recent literature.

Neuroendocrine differentiation of LNCaP cells suggests: VDAC in the cell membrane is involved in the extrinsic apoptotic pathway.

The primary structure of native human type-1 voltage dependent anion-selective channel/porin was presented twenty years ago, so was first data on its extra-mitochondrial expression in cell membranes of lymphocytes. Then, the channel had already entered cancer research as the docking molecule for hexokinase at outer mitochondrial membrane. Cell membrane standing porin met the cancer field only four years ago, when it was reported that normal and cancerous prostate cells from a single patient differed in the expression level of the channel.