Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes

A major route for the influx of calcium ions into neurons uses the STIM-Orai1 voltage-independent channel. Once cytosolic calcium ([Ca<sup>2+</sup>]i) elevates, it activates mitochondrial and endoplasmic calcium stores to affect downstream molecular pathways. In the present study, we emp...

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Main Authors: Liliia Kushnireva, Eduard Korkotian, Menahem Segal
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/16/12940
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author Liliia Kushnireva
Eduard Korkotian
Menahem Segal
author_facet Liliia Kushnireva
Eduard Korkotian
Menahem Segal
author_sort Liliia Kushnireva
collection DOAJ
description A major route for the influx of calcium ions into neurons uses the STIM-Orai1 voltage-independent channel. Once cytosolic calcium ([Ca<sup>2+</sup>]i) elevates, it activates mitochondrial and endoplasmic calcium stores to affect downstream molecular pathways. In the present study, we employed a novel drug, carbonyl cyanide chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, to explore the role of mitochondria in cultured neuronal morphology. CCCP caused a sustained elevation of [Ca<sup>2+</sup>]i and, quite surprisingly, a massive increase in the density of dendritic filopodia and spines in the affected neurons. This morphological change can be prevented in cultures exposed to a calcium-free medium, Orai1 antagonist 2APB, or cells transfected with a mutant Orai1 plasmid. It is suggested that CCCP activates mitochondria through the influx of calcium to cause rapid growth of dendritic processes.
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spelling doaj.art-995898fb73fb438383ebafbddfe58aad2023-11-19T01:32:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161294010.3390/ijms241612940Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic ProcessesLiliia Kushnireva0Eduard Korkotian1Menahem Segal2Faculty of Biology, Perm State University, 614068 Perm, RussiaDepartment of Brain Sciences, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Brain Sciences, Weizmann Institute of Science, Rehovot 7610001, IsraelA major route for the influx of calcium ions into neurons uses the STIM-Orai1 voltage-independent channel. Once cytosolic calcium ([Ca<sup>2+</sup>]i) elevates, it activates mitochondrial and endoplasmic calcium stores to affect downstream molecular pathways. In the present study, we employed a novel drug, carbonyl cyanide chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, to explore the role of mitochondria in cultured neuronal morphology. CCCP caused a sustained elevation of [Ca<sup>2+</sup>]i and, quite surprisingly, a massive increase in the density of dendritic filopodia and spines in the affected neurons. This morphological change can be prevented in cultures exposed to a calcium-free medium, Orai1 antagonist 2APB, or cells transfected with a mutant Orai1 plasmid. It is suggested that CCCP activates mitochondria through the influx of calcium to cause rapid growth of dendritic processes.https://www.mdpi.com/1422-0067/24/16/12940carbonyl cyanide chlorophenylhydrazone (CCCP)calciumOrai1STIM1dendritic processesmitochondria
spellingShingle Liliia Kushnireva
Eduard Korkotian
Menahem Segal
Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes
International Journal of Molecular Sciences
carbonyl cyanide chlorophenylhydrazone (CCCP)
calcium
Orai1
STIM1
dendritic processes
mitochondria
title Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes
title_full Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes
title_fullStr Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes
title_full_unstemmed Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes
title_short Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes
title_sort exposure of cultured hippocampal neurons to the mitochondrial uncoupler carbonyl cyanide chlorophenylhydrazone induces a rapid growth of dendritic processes
topic carbonyl cyanide chlorophenylhydrazone (CCCP)
calcium
Orai1
STIM1
dendritic processes
mitochondria
url https://www.mdpi.com/1422-0067/24/16/12940
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