| First Author | Gergalova G | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 2 | Pages | e31361 |
| PubMed ID | 22359587 | Mgi Jnum | J:224056 |
| Mgi Id | MGI:5661143 | Doi | 10.1371/journal.pone.0031361 |
| Citation | Gergalova G, et al. (2012) Mitochondria express alpha7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria. PLoS One 7(2):e31361 |
| abstractText | Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that mediate synaptic transmission in the muscle and autonomic ganglia and regulate transmitter release in the brain. The nAChRs composed of alpha7 subunits are also expressed in non-excitable cells to regulate cell survival and proliferation. Up to now, functional alpha7 nAChRs were found exclusively on the cell plasma membrane. Here we show that they are expressed in mitochondria and regulate early pro-apoptotic events like cytochrome c release. The binding of alpha7-specific antibody with mouse liver mitochondria was revealed by electron microscopy. Outer membranes of mitochondria from the wild-type and beta2-/- but not alpha7-/- mice bound alpha7 nAChR-specific antibody and toxins: FITC-labeled alpha-cobratoxin or Alexa 555-labeled alpha-bungarotoxin. alpha7 nAChR agonists (1 microM acetylcholine, 10 microM choline or 30 nM PNU-282987) impaired intramitochondrial Ca(2+) accumulation and significantly decreased cytochrome c release stimulated with either 90 microM CaCl(2) or 0.5 mM H(2)O(2). alpha7-specific antagonist methyllicaconitine (50 nM) did not affect Ca(2+) accumulation in mitochondria but attenuated the effects of agonists on cytochrome c release. Inhibitor of voltage-dependent anion channel (VDAC) 4,4'-diisothio-cyano-2,2'-stilbene disulfonic acid (0.5 microM) decreased cytochrome c release stimulated with apoptogens similarly to alpha7 nAChR agonists, and VDAC was co-captured with the alpha7 nAChR from mitochondria outer membrane preparation in both direct and reverse sandwich ELISA. It is concluded that alpha7 nAChRs are expressed in mitochondria outer membrane to regulate the VDAC-mediated Ca(2+) transport and mitochondrial permeability transition. |
