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closeInflammasome and VDAC
Posted by fripthin on 05 Dec 2012 at 17:50 GMT
Mitochondrial respiration has been inhibited by knocking down the expression of voltage-dependent anion channels (VDAC).
In cells lacking VDACs, IL-1β production and caspase-1 activation were abrogated in response to NLRP3 activators.
Similarly, cells overexpressing Bcl-2, which inhibits VDAC function, also displayed impaired production of IL-1β in response to MSU, alum or nigericin (1,2).
It might be worth to consider, that cell membrane standing type-1 VDAC can be blocked by extracellular application of BH4 Bcl-XL domain peptides (3-5),
likely via a C-terminal ATP-binding motif (6), missing in Bcl-2.
1) Sorbara MT, Girardin SE. Mitochondrial ROS fuel the inflammasome. Cell Res. 2011, 21:558-60.
2) Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2010; 469:221-225.
3) Thinnes FP, Hellmann KP, Hilschmann N. Blockade of regulatory volume decrease (RVD) of HeLa cells by extracellularly applied BH4 domain peptides of anti-apoptotic BCI-XL. Pflügers Arch – Eur J Physiol. 2001; 441, Supplement No. 6: R137
4) Thinnes FP, Burckhardt G. On a fully closed state of native human type-1 VDAC enriched in Nonidet P40. Mol Genet Metab. 2012; 107:632-633.
5) 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; 161:274-6.
6) Chen K, Mizianty MJ, Kurgan L. Prediction and analysis of nucleotide-binding residues using sequence and sequence-derived structural descriptors. Bioinformatics 2012; 28:331-341.