ParkinsonFranceV1, Main, Exploration, bibRecord, 000922

Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

Identifieur interne : 000922 ( Main/Exploration ); précédent : 000921; suivant : 000923

Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

Auteurs : Rubén G Mez-Sánchez [Espagne] ; Matthew E. Gegg [Royaume-Uni] ; José M. Bravo-San Pedro [Espagne, France] ; Mireia Niso-Santano [Espagne, France] ; Lydia Alvarez-Erviti [Royaume-Uni] ; Elisa Pizarro-Estrella [Espagne] ; Yolanda Gutiérrez-Martín [Espagne] ; Alberto Alvarez-Barrientos [Espagne] ; José M. Fuentes [Espagne] ; Rosa Ana González-Polo [Espagne] ; Anthony H. V. Schapira [Royaume-Uni]

Source :

Neurobiology of Disease [ 0969-9961 ] ; 2014.

RBID : PMC:3898697

English descriptors

KwdEn :
- Autophagy (drug effects), Calcium (metabolism), Carbonyl Cyanide m-Chlorophenyl Hydrazone (toxicity), Cell Line, Tumor, Gene Expression, Humans, Mitochondria (drug effects), Mitochondria (enzymology), Mitochondria (metabolism), Mitochondrial Degradation (drug effects), Mitochondrial Degradation (physiology), Neuroblastoma (enzymology), Neuroblastoma (metabolism), Protein Kinases (genetics), Protein Kinases (metabolism), Proto-Oncogene Proteins c-fos (metabolism), Proton Ionophores (toxicity).
MESH :
- chemical , genetics : Protein Kinases.
- chemical , metabolism : Calcium, Protein Kinases, Proto-Oncogene Proteins c-fos.
- drug effects : Autophagy, Mitochondria, Mitochondrial Degradation.
- enzymology : Mitochondria, Neuroblastoma.
- metabolism : Mitochondria, Neuroblastoma.
- physiology : Mitochondrial Degradation.
- chemical , toxicity : Carbonyl Cyanide m-Chlorophenyl Hydrazone, Proton Ionophores.
- Cell Line, Tumor, Gene Expression, Humans.

Abstract

Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24 h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3 h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898697

DOI: 10.1016/j.nbd.2013.10.021
PubMed: 24184327
PubMed Central: 3898697

Affiliations:

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression<sup><xref ref-type="fn" rid="d32e773">☆</xref>
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<author><name sortKey="Alvarez Erviti, Lydia" sort="Alvarez Erviti, Lydia" uniqKey="Alvarez Erviti L" first="Lydia" last="Alvarez-Erviti">Lydia Alvarez-Erviti</name>
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<author><name sortKey="Gutierrez Martin, Yolanda" sort="Gutierrez Martin, Yolanda" uniqKey="Gutierrez Martin Y" first="Yolanda" last="Gutiérrez-Martín">Yolanda Gutiérrez-Martín</name>
<affiliation wicri:level="4"><nlm:aff id="af0020">Servicio de Técnicas Aplicadas a las Biociencias, Universidad de Extremadura, 06071 Badajoz, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
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<placeName><region nuts="2" type="communauté">Estrémadure</region>
<settlement type="city">Mérida (Espagne)</settlement>
</placeName>
<orgName type="university">Université d'Estrémadure</orgName>
</affiliation>
</author>
<author><name sortKey="Alvarez Barrientos, Alberto" sort="Alvarez Barrientos, Alberto" uniqKey="Alvarez Barrientos A" first="Alberto" last="Alvarez-Barrientos">Alberto Alvarez-Barrientos</name>
<affiliation wicri:level="4"><nlm:aff id="af0020">Servicio de Técnicas Aplicadas a las Biociencias, Universidad de Extremadura, 06071 Badajoz, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Servicio de Técnicas Aplicadas a las Biociencias, Universidad de Extremadura, 06071 Badajoz</wicri:regionArea>
<placeName><region nuts="2" type="communauté">Estrémadure</region>
<settlement type="city">Mérida (Espagne)</settlement>
</placeName>
<orgName type="university">Université d'Estrémadure</orgName>
</affiliation>
</author>
<author><name sortKey="Fuentes, Jose M" sort="Fuentes, Jose M" uniqKey="Fuentes J" first="José M." last="Fuentes">José M. Fuentes</name>
<affiliation wicri:level="4"><nlm:aff id="af0005">Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, F. Enfermería y Terapia Ocupacional, 10003 Cáceres, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, F. Enfermería y Terapia Ocupacional, 10003 Cáceres</wicri:regionArea>
<placeName><region nuts="2" type="communauté">Estrémadure</region>
<settlement type="city">Mérida (Espagne)</settlement>
</placeName>
<orgName type="university">Université d'Estrémadure</orgName>
</affiliation>
</author>
<author><name sortKey="Gonzalez Polo, Rosa Ana" sort="Gonzalez Polo, Rosa Ana" uniqKey="Gonzalez Polo R" first="Rosa Ana" last="González-Polo">Rosa Ana González-Polo</name>
<affiliation wicri:level="4"><nlm:aff id="af0005">Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, F. Enfermería y Terapia Ocupacional, 10003 Cáceres, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, F. Enfermería y Terapia Ocupacional, 10003 Cáceres</wicri:regionArea>
<placeName><region nuts="2" type="communauté">Estrémadure</region>
<settlement type="city">Mérida (Espagne)</settlement>
</placeName>
<orgName type="university">Université d'Estrémadure</orgName>
</affiliation>
</author>
<author><name sortKey="Schapira, Anthony H V" sort="Schapira, Anthony H V" uniqKey="Schapira A" first="Anthony H. V." last="Schapira">Anthony H. V. Schapira</name>
<affiliation wicri:level="4"><nlm:aff id="af0010">Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF</wicri:regionArea>
<orgName type="university">University College de Londres</orgName>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
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<series><title level="j">Neurobiology of Disease</title>
<idno type="ISSN">0969-9961</idno>
<idno type="eISSN">1095-953X</idno>
<imprint><date when="2014">2014</date>
</imprint>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Autophagy (drug effects)</term>
<term>Calcium (metabolism)</term>
<term>Carbonyl Cyanide m-Chlorophenyl Hydrazone (toxicity)</term>
<term>Cell Line, Tumor</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Mitochondria (drug effects)</term>
<term>Mitochondria (enzymology)</term>
<term>Mitochondria (metabolism)</term>
<term>Mitochondrial Degradation (drug effects)</term>
<term>Mitochondrial Degradation (physiology)</term>
<term>Neuroblastoma (enzymology)</term>
<term>Neuroblastoma (metabolism)</term>
<term>Protein Kinases (genetics)</term>
<term>Protein Kinases (metabolism)</term>
<term>Proto-Oncogene Proteins c-fos (metabolism)</term>
<term>Proton Ionophores (toxicity)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium</term>
<term>Protein Kinases</term>
<term>Proto-Oncogene Proteins c-fos</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term>
<term>Mitochondria</term>
<term>Mitochondrial Degradation</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Mitochondria</term>
<term>Neuroblastoma</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Mitochondria</term>
<term>Neuroblastoma</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Mitochondrial Degradation</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Carbonyl Cyanide m-Chlorophenyl Hydrazone</term>
<term>Proton Ionophores</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term>
<term>Gene Expression</term>
<term>Humans</term>
</keywords>
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<front><div type="abstract" xml:lang="en"><p>Mutations of the <italic>PTEN-induced kinase 1 (PINK1)</italic>
 gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24 h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3 h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection.</p>
</div>
</front>
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</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Youle, R J" uniqKey="Youle R">R.J. Youle</name>
</author>
<author><name sortKey="Narendra, D P" uniqKey="Narendra D">D.P. Narendra</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhao, R" uniqKey="Zhao R">R. Zhao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhou, C" uniqKey="Zhou C">C. Zhou</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ziviani, E" uniqKey="Ziviani E">E. Ziviani</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zucker, R S" uniqKey="Zucker R">R.S. Zucker</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Espagne</li>
<li>France</li>
<li>Royaume-Uni</li>
</country>
<region><li>Angleterre</li>
<li>Estrémadure</li>
<li>Grand Londres</li>
<li>Île-de-France</li>
</region>
<settlement><li>Londres</li>
<li>Mérida (Espagne)</li>
<li>Villejuif</li>
</settlement>
<orgName><li>University College de Londres</li>
<li>Université Paris-Sud</li>
<li>Université d'Estrémadure</li>
</orgName>
</list>
<tree><country name="Espagne"><region name="Estrémadure"><name sortKey="G Mez Sanchez, Ruben" sort="G Mez Sanchez, Ruben" uniqKey="G Mez Sanchez R" first="Rubén" last="G Mez-Sánchez">Rubén G Mez-Sánchez</name>
</region>
<name sortKey="Alvarez Barrientos, Alberto" sort="Alvarez Barrientos, Alberto" uniqKey="Alvarez Barrientos A" first="Alberto" last="Alvarez-Barrientos">Alberto Alvarez-Barrientos</name>
<name sortKey="Bravo San Pedro, Jose M" sort="Bravo San Pedro, Jose M" uniqKey="Bravo San Pedro J" first="José M." last="Bravo-San Pedro">José M. Bravo-San Pedro</name>
<name sortKey="Fuentes, Jose M" sort="Fuentes, Jose M" uniqKey="Fuentes J" first="José M." last="Fuentes">José M. Fuentes</name>
<name sortKey="Gonzalez Polo, Rosa Ana" sort="Gonzalez Polo, Rosa Ana" uniqKey="Gonzalez Polo R" first="Rosa Ana" last="González-Polo">Rosa Ana González-Polo</name>
<name sortKey="Gutierrez Martin, Yolanda" sort="Gutierrez Martin, Yolanda" uniqKey="Gutierrez Martin Y" first="Yolanda" last="Gutiérrez-Martín">Yolanda Gutiérrez-Martín</name>
<name sortKey="Niso Santano, Mireia" sort="Niso Santano, Mireia" uniqKey="Niso Santano M" first="Mireia" last="Niso-Santano">Mireia Niso-Santano</name>
<name sortKey="Pizarro Estrella, Elisa" sort="Pizarro Estrella, Elisa" uniqKey="Pizarro Estrella E" first="Elisa" last="Pizarro-Estrella">Elisa Pizarro-Estrella</name>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Gegg, Matthew E" sort="Gegg, Matthew E" uniqKey="Gegg M" first="Matthew E." last="Gegg">Matthew E. Gegg</name>
</region>
<name sortKey="Alvarez Erviti, Lydia" sort="Alvarez Erviti, Lydia" uniqKey="Alvarez Erviti L" first="Lydia" last="Alvarez-Erviti">Lydia Alvarez-Erviti</name>
<name sortKey="Schapira, Anthony H V" sort="Schapira, Anthony H V" uniqKey="Schapira A" first="Anthony H. V." last="Schapira">Anthony H. V. Schapira</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Bravo San Pedro, Jose M" sort="Bravo San Pedro, Jose M" uniqKey="Bravo San Pedro J" first="José M." last="Bravo-San Pedro">José M. Bravo-San Pedro</name>
</region>
<name sortKey="Niso Santano, Mireia" sort="Niso Santano, Mireia" uniqKey="Niso Santano M" first="Mireia" last="Niso-Santano">Mireia Niso-Santano</name>
</country>
</tree>
</affiliations>
</record>

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HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000922 | SxmlIndent | more

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{{Explor lien
   |wiki=    Wicri/Sante
   |area=    ParkinsonFranceV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:3898697
   |texte=   Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆
}}

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Data generation: Wed May 17 19:46:39 2017. Site generation: Mon Mar 4 15:48:15 2024

La maladie de Parkinson en France (serveur d'exploration)

Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

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Abstract

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Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	La maladie de Parkinson en France (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.