α7 nicotinic acetylcholine receptors control cytochrome c release from isolated mitochondria through kinase-mediated pathways

Nicotinic Acetylcholine Receptor-Mediated Protection of the Rat Heart Exposed to Ischemia Reperfusion

“…Dvorakova et al (10) showed by immunohistochemistry of rat hearts that nicotinic α7 subunits localize to cardiac neurons, fibroblasts and cardiomyocytes, and that α2/α4 subunits concentrate at myocyte intercalated discs. More recently, Gergalova et al (11,12) identified α7nAChRs in liver mitochondria outer membranes that function to regulate mitochondrial permeability transition pore (mPTP) formation through kinasemediated signaling pathways, thus preventing cytochrome c release and attenuating apoptosis. The presence of α7nAChRs in cardiac mitochondria has not been reported.…”

Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death

“…Although the nAChR is conserved across vertebrates and invertebrates, the diverse composition and assembly of α-(containing two adjacent cysteine residues important in ACh binding) and non α-(lacking the cysteine residues) subunits confer diverse functional architecture and, therefore, toxicological responses (Jones and Sattelle, 2010). Interestingly, in mammals, nAChRs have been shown to be expressed in the outer membranes of mitochondria, with subtypes having tissue-specific locations Gergalova et al, 2014;Kalashnyk et al, 2012;Lykhmus et al, 2014). For example, in mice, brain and liver mitochondria typically express α7β2 and α4β2 nAChRs, whereas lung predominantly express α3β2 nAChRs .…”

“…In mammals, nAChRs have been identified on the mitochondrial outer membrane, providing plausibility that perturbation of the nAChR by a chemical stressor could lead to impacts on the mitochondria Gergalova et al, 2014;Kalashnyk et al, 2012;Lykhmus et al, 2014). Further, studies with both honey bees and bumble bees (Bombus terrestris) demonstrate adverse impacts on mitochondria when exposed to nAChR agonists (Moffat et al, 2015;Nicodemo et al, 2014).…”

“…provided evidence that these receptors are coupled with the voltage dependent anion-selective channel . In mouse brain and liver, agonists of the nAChR have been shown to prevent Ca 2+ -evoked apoptosis by interfering with intra-mitochondrial kinases (particularly phosphatidylinositol-3-kinase/Akt signaling pathway), effectively attenuating cytochrome c release by preventing oligomerization of voltage dependent anion-selective channel and preventing its involvement in mitochondria permeability transition pore formation Gergalova et al, 2014). In this case, nAChR activation leading to mitochondrial dysfunction was captured via interference with apoptotic events.…”

Critical Role of the Neonatal Fc Receptor (FcRn) in the Pathogenic Action of Antimitochondrial Autoantibodies Synergizing with Anti-desmoglein Autoantibodies in Pemphigus Vulgaris

“…One possible mechanism involves phosphorylation of VDAC1, because changes of VDAC1 phosphorylation status cause a similar effect (32,33). Furthermore, AMA binding to mitochondrial nicotinic acetylcholine receptors, which both associate with VDAC and activate protein kinases (34,35), can cause mitochondrial permeability transition pore opening (13). Therefore, we hypothesized that VDAC1 might be associated with AMA in multiprotein complexes.…”