Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.

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 α7 subunits are also expressed in non-excitable cells to regulate cell survival and pr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Galyna Gergalova, Olena Lykhmus, Olena Kalashnyk, Lyudmyla Koval, Volodymyr Chernyshov, Elena Kryukova, Victor Tsetlin, Sergiy Komisarenko, Maryna Skok
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8c0db0ecc4544ec826a32204e9edf14
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f8c0db0ecc4544ec826a32204e9edf14
record_format	dspace
spelling	oai:doaj.org-article:f8c0db0ecc4544ec826a32204e9edf142021-11-18T07:28:00ZMitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.1932-620310.1371/journal.pone.0031361https://doaj.org/article/f8c0db0ecc4544ec826a32204e9edf142012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22359587/?tool=EBIhttps://doaj.org/toc/1932-6203Nicotinic 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 α7 subunits are also expressed in non-excitable cells to regulate cell survival and proliferation. Up to now, functional α7 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 α7-specific antibody with mouse liver mitochondria was revealed by electron microscopy. Outer membranes of mitochondria from the wild-type and β2-/- but not α7-/- mice bound α7 nAChR-specific antibody and toxins: FITC-labeled α-cobratoxin or Alexa 555-labeled α-bungarotoxin. α7 nAChR agonists (1 µM acetylcholine, 10 µM choline or 30 nM PNU-282987) impaired intramitochondrial Ca(2+) accumulation and significantly decreased cytochrome c release stimulated with either 90 µM CaCl(2) or 0.5 mM H(2)O(2). α7-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 µM) decreased cytochrome c release stimulated with apoptogens similarly to α7 nAChR agonists, and VDAC was co-captured with the α7 nAChR from mitochondria outer membrane preparation in both direct and reverse sandwich ELISA. It is concluded that α7 nAChRs are expressed in mitochondria outer membrane to regulate the VDAC-mediated Ca(2+) transport and mitochondrial permeability transition.Galyna GergalovaOlena LykhmusOlena KalashnykLyudmyla KovalVolodymyr ChernyshovElena KryukovaVictor TsetlinSergiy KomisarenkoMaryna SkokPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31361 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Galyna Gergalova Olena Lykhmus Olena Kalashnyk Lyudmyla Koval Volodymyr Chernyshov Elena Kryukova Victor Tsetlin Sergiy Komisarenko Maryna Skok Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.
description	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 α7 subunits are also expressed in non-excitable cells to regulate cell survival and proliferation. Up to now, functional α7 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 α7-specific antibody with mouse liver mitochondria was revealed by electron microscopy. Outer membranes of mitochondria from the wild-type and β2-/- but not α7-/- mice bound α7 nAChR-specific antibody and toxins: FITC-labeled α-cobratoxin or Alexa 555-labeled α-bungarotoxin. α7 nAChR agonists (1 µM acetylcholine, 10 µM choline or 30 nM PNU-282987) impaired intramitochondrial Ca(2+) accumulation and significantly decreased cytochrome c release stimulated with either 90 µM CaCl(2) or 0.5 mM H(2)O(2). α7-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 µM) decreased cytochrome c release stimulated with apoptogens similarly to α7 nAChR agonists, and VDAC was co-captured with the α7 nAChR from mitochondria outer membrane preparation in both direct and reverse sandwich ELISA. It is concluded that α7 nAChRs are expressed in mitochondria outer membrane to regulate the VDAC-mediated Ca(2+) transport and mitochondrial permeability transition.
format	article
author	Galyna Gergalova Olena Lykhmus Olena Kalashnyk Lyudmyla Koval Volodymyr Chernyshov Elena Kryukova Victor Tsetlin Sergiy Komisarenko Maryna Skok
author_facet	Galyna Gergalova Olena Lykhmus Olena Kalashnyk Lyudmyla Koval Volodymyr Chernyshov Elena Kryukova Victor Tsetlin Sergiy Komisarenko Maryna Skok
author_sort	Galyna Gergalova
title	Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.
title_short	Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.
title_full	Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.
title_fullStr	Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.
title_full_unstemmed	Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.
title_sort	mitochondria express α7 nicotinic acetylcholine receptors to regulate ca2+ accumulation and cytochrome c release: study on isolated mitochondria.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f8c0db0ecc4544ec826a32204e9edf14
work_keys_str_mv	AT galynagergalova mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria AT olenalykhmus mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria AT olenakalashnyk mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria AT lyudmylakoval mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria AT volodymyrchernyshov mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria AT elenakryukova mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria AT victortsetlin mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria AT sergiykomisarenko mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria AT marynaskok mitochondriaexpressa7nicotinicacetylcholinereceptorstoregulateca2accumulationandcytochromecreleasestudyonisolatedmitochondria
_version_	1718423448969019392

Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria.

Ejemplares similares