α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson’s disease
This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human α-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, α-synuclein does not seem to have any significant effect on the activiti...
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| Veröffentlicht in: | FEBS letters 2010-04, Vol.584 (8), p.1571-1576 |
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| creator | Banerjee, Kalpita Sinha, Maitrayee Pham, Chi Le Lan Jana, Sirsendu Chanda, Dalia Cappai, Roberto Chakrabarti, Sasanka |
| description | This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human α-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, α-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type α-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria. The results are significant in view of the fact that α-synucleinopathy is involved in the pathogenesis of Parkinson’s disease. |
| doi_str_mv | 10.1016/j.febslet.2010.03.012 |
| format | Article |
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However, α-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type α-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria. The results are significant in view of the fact that α-synucleinopathy is involved in the pathogenesis of Parkinson’s disease.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/j.febslet.2010.03.012</identifier><identifier>PMID: 20226185</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>alpha-Synuclein - genetics ; alpha-Synuclein - pharmacology ; Animals ; Brain - cytology ; Brain - pathology ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Dopamine ; Dose-Response Relationship, Drug ; Electron Transport - drug effects ; Humans ; Membrane potential ; Membrane Potential, Mitochondrial - drug effects ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mutation ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Parkinson's disease ; Phosphorylation ; Phosphorylation - drug effects ; Rats ; α-Synuclein</subject><ispartof>FEBS letters, 2010-04, Vol.584 (8), p.1571-1576</ispartof><rights>2010 Federation of European Biochemical Societies</rights><rights>FEBS Letters 584 (2010) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><rights>Copyright 2010 Federation of European Biochemical Societies. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4761-19966ce65fe0626a47160f1d60ab8c5cdf70c57779568f60b1a2d171535a07283</citedby><cites>FETCH-LOGICAL-c4761-19966ce65fe0626a47160f1d60ab8c5cdf70c57779568f60b1a2d171535a07283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.febslet.2010.03.012$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014579310002061$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,1427,3537,27901,27902,45550,45551,46384,46808,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20226185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Banerjee, Kalpita</creatorcontrib><creatorcontrib>Sinha, Maitrayee</creatorcontrib><creatorcontrib>Pham, Chi Le Lan</creatorcontrib><creatorcontrib>Jana, Sirsendu</creatorcontrib><creatorcontrib>Chanda, Dalia</creatorcontrib><creatorcontrib>Cappai, Roberto</creatorcontrib><creatorcontrib>Chakrabarti, Sasanka</creatorcontrib><title>α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson’s disease</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human α-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, α-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type α-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria. The results are significant in view of the fact that α-synucleinopathy is involved in the pathogenesis of Parkinson’s disease.</description><subject>alpha-Synuclein - genetics</subject><subject>alpha-Synuclein - pharmacology</subject><subject>Animals</subject><subject>Brain - cytology</subject><subject>Brain - pathology</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Dopamine</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electron Transport - drug effects</subject><subject>Humans</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mutation</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson Disease - pathology</subject><subject>Parkinson's disease</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Rats</subject><subject>α-Synuclein</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFu1TAQhi0Eoq-FI4C8Y5WH7bzYCRtEq5ZWqgRSYW059kT1w7GDnYDCimtUnIKLcAhOgkMebGFhWZ75_3-s-RB6QsmWEsqf77cdtMnBuGUk10i5JZTdQxtai7Iod7y-jzaE0F1RiaY8Qscp7Ul-17R5iI4YYYzTutqgbz--Fzezn7QD67H1ZtJgcA99G5UHbGAITkX7RY02eKy8wS6khEOHh9uQ8omzW3taDUrbcV56NmXXmIOiGnFOytG9HYO-Dd5Eq17gq35wVv82pjwVv1Xxg_Up-J9f7xI2NoFK8Ag96JRL8Phwn6D3F-fvzi6L6zevr85eXRd6JzgtaNNwroFXHRDOuNoJyklHDSeqrXWlTSeIroQQTcXrjpOWKmaooFVZKSJYXZ6gZ2vuEMPHCdIoe5s0OJc3EKYkRVnWvGlYk5XVqtQxbyFCJ4doexVnSYlcsMi9PGCRCxZJSpmxZN_Tw4Sp7cH8df3hkAWXq-CzdTD_X6q8OD9lNwvjBTHNdBnhNEe9XKMgr-yThSiTtuAzVhtBj9IE-4_f_gKTE7sm</recordid><startdate>20100416</startdate><enddate>20100416</enddate><creator>Banerjee, Kalpita</creator><creator>Sinha, Maitrayee</creator><creator>Pham, Chi Le Lan</creator><creator>Jana, Sirsendu</creator><creator>Chanda, Dalia</creator><creator>Cappai, Roberto</creator><creator>Chakrabarti, Sasanka</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100416</creationdate><title>α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson’s disease</title><author>Banerjee, Kalpita ; Sinha, Maitrayee ; Pham, Chi Le Lan ; Jana, Sirsendu ; Chanda, Dalia ; Cappai, Roberto ; Chakrabarti, Sasanka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4761-19966ce65fe0626a47160f1d60ab8c5cdf70c57779568f60b1a2d171535a07283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>alpha-Synuclein - genetics</topic><topic>alpha-Synuclein - pharmacology</topic><topic>Animals</topic><topic>Brain - cytology</topic><topic>Brain - pathology</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Dopamine</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electron Transport - drug effects</topic><topic>Humans</topic><topic>Membrane potential</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mutation</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson Disease - pathology</topic><topic>Parkinson's disease</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Rats</topic><topic>α-Synuclein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Banerjee, Kalpita</creatorcontrib><creatorcontrib>Sinha, Maitrayee</creatorcontrib><creatorcontrib>Pham, Chi Le Lan</creatorcontrib><creatorcontrib>Jana, Sirsendu</creatorcontrib><creatorcontrib>Chanda, Dalia</creatorcontrib><creatorcontrib>Cappai, Roberto</creatorcontrib><creatorcontrib>Chakrabarti, Sasanka</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Banerjee, Kalpita</au><au>Sinha, Maitrayee</au><au>Pham, Chi Le Lan</au><au>Jana, Sirsendu</au><au>Chanda, Dalia</au><au>Cappai, Roberto</au><au>Chakrabarti, Sasanka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson’s disease</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2010-04-16</date><risdate>2010</risdate><volume>584</volume><issue>8</issue><spage>1571</spage><epage>1576</epage><pages>1571-1576</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human α-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, α-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type α-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria. The results are significant in view of the fact that α-synucleinopathy is involved in the pathogenesis of Parkinson’s disease.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>20226185</pmid><doi>10.1016/j.febslet.2010.03.012</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | alpha-Synuclein - genetics alpha-Synuclein - pharmacology Animals Brain - cytology Brain - pathology Cell Membrane - drug effects Cell Membrane - metabolism Dopamine Dose-Response Relationship, Drug Electron Transport - drug effects Humans Membrane potential Membrane Potential, Mitochondrial - drug effects Mitochondria Mitochondria - drug effects Mitochondria - metabolism Mutation Parkinson Disease - metabolism Parkinson Disease - pathology Parkinson's disease Phosphorylation Phosphorylation - drug effects Rats α-Synuclein |
| title | α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson’s disease |
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