The mitochondria-targeted derivative of the classical uncoupler of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone is an effective mitochondrial recoupler
The synthesis of a mitochondria-targeted derivative of the classical mitochondrial uncoupler carbonyl cyanide-m-chlorophenylhydrazone (CCCP) by alkoxy substitution of CCCP with n-decyl(triphenyl)phosphonium cation yielded mitoCCCP, which was able to inhibit the uncoupling action of CCCP, tyrphostin...
Gespeichert in:
| Veröffentlicht in: | PloS one 2020-12, Vol.15 (12), p.e0244499-e0244499 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0244499 |
|---|---|
| container_issue | 12 |
| container_start_page | e0244499 |
| container_title | PloS one |
| container_volume | 15 |
| creator | Iaubasarova, Iliuza R Khailova, Ljudmila S Firsov, Alexander M Grivennikova, Vera G Kirsanov, Roman S Korshunova, Galina A Kotova, Elena A Antonenko, Yuri N |
| description | The synthesis of a mitochondria-targeted derivative of the classical mitochondrial uncoupler carbonyl cyanide-m-chlorophenylhydrazone (CCCP) by alkoxy substitution of CCCP with n-decyl(triphenyl)phosphonium cation yielded mitoCCCP, which was able to inhibit the uncoupling action of CCCP, tyrphostin A9 and niclosamide on rat liver mitochondria, but not that of 2,4-dinitrophenol, at a concentration of 1-2 μM. MitoCCCP did not uncouple mitochondria by itself at these concentrations, although it exhibited uncoupling action at tens of micromolar concentrations. Thus, mitoCCCP appeared to be a more effective mitochondrial recoupler than 6-ketocholestanol. Both mitoCCCP and 6-ketocholestanol did not inhibit the protonophoric activity of CCCP in artificial bilayer lipid membranes, which might compromise the simple proton-shuttling mechanism of the uncoupling activity on mitochondria. |
| doi_str_mv | 10.1371/journal.pone.0244499 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2474249037</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A647081002</galeid><doaj_id>oai_doaj_org_article_06c2b5d970a34d868e4289644bb2430a</doaj_id><sourcerecordid>A647081002</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-768eff639c535ad6ecfcaec2f801262f55faa3403ca715a3484c312d3a1b5f8d3</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7jr6D0QLguhFxzRJv26EZfFjYGFBV2_DaT6mWTLJmLTDjv_J_2i6012mshcSStOT57zvSdKTJC9ztMxJlX-4doO3YJZbZ-USYUpp0zxKTvOG4KzEiDw-mp8kz0K4RqggdVk-TU4IIVVNc3qa_LnqZLrRveOds8JryHrwa9lLkQrp9Q56vZOpU2kfOW4gBM3BpIPlbtga6ccld6PFgdt2LsTH7038djbl4Ftn9yble7BaRKeMd8Z5t-1kDHd74eF3rD_VIQWbSqUkvxU6rsikXk5uz5MnCkyQL6b3Ivnx-dPV-dfs4vLL6vzsIuNlg_usKusoVZKGF6QAUUquOEiOVY1yXGJVFAqAUEQ4VHkRZzXlJMeCQN4WqhZkkbw-6G6NC2w66cAwrSimDSJVJFYHQji4ZluvN-D3zIFmtwHn1wx8r7mRDJUct4VoKhSdRB1ro7huSkrbFlMSg4vk4-Q2tBspuLS9BzMTna9Y3bG127GqqgiOY5G8mwS8-zXI0LONDlwaA1a64VA3baoG1RF98w_68O4mag1xA9oqF335KMrOSlqhOkdotF0-QMUh5EbzeK1Kx_gs4f0sITK9vOnXMITAVt-__T97-XPOvj1iOwmm74Izw_gPhjlIDyD3LgQv1f0h54iNXXV3GmzsKjZ1VUx7dXxB90l3bUT-ArdmIjA</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2474249037</pqid></control><display><type>article</type><title>The mitochondria-targeted derivative of the classical uncoupler of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone is an effective mitochondrial recoupler</title><source>Directory of Open Access Journals (DOAJ)</source><source>MEDLINE</source><source>Public Library of Science</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>EZB Electronic Journals Library</source><creator>Iaubasarova, Iliuza R ; Khailova, Ljudmila S ; Firsov, Alexander M ; Grivennikova, Vera G ; Kirsanov, Roman S ; Korshunova, Galina A ; Kotova, Elena A ; Antonenko, Yuri N</creator><creatorcontrib>Iaubasarova, Iliuza R ; Khailova, Ljudmila S ; Firsov, Alexander M ; Grivennikova, Vera G ; Kirsanov, Roman S ; Korshunova, Galina A ; Kotova, Elena A ; Antonenko, Yuri N</creatorcontrib><description>The synthesis of a mitochondria-targeted derivative of the classical mitochondrial uncoupler carbonyl cyanide-m-chlorophenylhydrazone (CCCP) by alkoxy substitution of CCCP with n-decyl(triphenyl)phosphonium cation yielded mitoCCCP, which was able to inhibit the uncoupling action of CCCP, tyrphostin A9 and niclosamide on rat liver mitochondria, but not that of 2,4-dinitrophenol, at a concentration of 1-2 μM. MitoCCCP did not uncouple mitochondria by itself at these concentrations, although it exhibited uncoupling action at tens of micromolar concentrations. Thus, mitoCCCP appeared to be a more effective mitochondrial recoupler than 6-ketocholestanol. Both mitoCCCP and 6-ketocholestanol did not inhibit the protonophoric activity of CCCP in artificial bilayer lipid membranes, which might compromise the simple proton-shuttling mechanism of the uncoupling activity on mitochondria.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0244499</identifier><identifier>PMID: 33378414</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>2,4-Dinitrophenol ; Animals ; Biology ; Biology and Life Sciences ; Carbonyl compounds ; Carbonyl Cyanide m-Chlorophenyl Hydrazone - analogs & derivatives ; Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology ; Carbonyls ; Cattle ; Cyanides ; E coli ; Ketocholesterols - pharmacology ; Lipid membranes ; Lipids ; Liver ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Membranes ; Mitochondria ; Mitochondria, Liver - drug effects ; Mitochondria, Liver - metabolism ; Niclosamide ; Oxidative Coupling - drug effects ; Oxidative phosphorylation ; Oxidative Phosphorylation - drug effects ; Phosphorylation ; Physical Sciences ; Physiological aspects ; Proteins ; Rats ; Respiration ; Uncoupling Agents - pharmacology</subject><ispartof>PloS one, 2020-12, Vol.15 (12), p.e0244499-e0244499</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Iaubasarova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Iaubasarova et al 2020 Iaubasarova et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-768eff639c535ad6ecfcaec2f801262f55faa3403ca715a3484c312d3a1b5f8d3</citedby><cites>FETCH-LOGICAL-c692t-768eff639c535ad6ecfcaec2f801262f55faa3403ca715a3484c312d3a1b5f8d3</cites><orcidid>0000-0002-0244-855X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773232/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773232/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33378414$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iaubasarova, Iliuza R</creatorcontrib><creatorcontrib>Khailova, Ljudmila S</creatorcontrib><creatorcontrib>Firsov, Alexander M</creatorcontrib><creatorcontrib>Grivennikova, Vera G</creatorcontrib><creatorcontrib>Kirsanov, Roman S</creatorcontrib><creatorcontrib>Korshunova, Galina A</creatorcontrib><creatorcontrib>Kotova, Elena A</creatorcontrib><creatorcontrib>Antonenko, Yuri N</creatorcontrib><title>The mitochondria-targeted derivative of the classical uncoupler of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone is an effective mitochondrial recoupler</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The synthesis of a mitochondria-targeted derivative of the classical mitochondrial uncoupler carbonyl cyanide-m-chlorophenylhydrazone (CCCP) by alkoxy substitution of CCCP with n-decyl(triphenyl)phosphonium cation yielded mitoCCCP, which was able to inhibit the uncoupling action of CCCP, tyrphostin A9 and niclosamide on rat liver mitochondria, but not that of 2,4-dinitrophenol, at a concentration of 1-2 μM. MitoCCCP did not uncouple mitochondria by itself at these concentrations, although it exhibited uncoupling action at tens of micromolar concentrations. Thus, mitoCCCP appeared to be a more effective mitochondrial recoupler than 6-ketocholestanol. Both mitoCCCP and 6-ketocholestanol did not inhibit the protonophoric activity of CCCP in artificial bilayer lipid membranes, which might compromise the simple proton-shuttling mechanism of the uncoupling activity on mitochondria.</description><subject>2,4-Dinitrophenol</subject><subject>Animals</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Carbonyl compounds</subject><subject>Carbonyl Cyanide m-Chlorophenyl Hydrazone - analogs & derivatives</subject><subject>Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology</subject><subject>Carbonyls</subject><subject>Cattle</subject><subject>Cyanides</subject><subject>E coli</subject><subject>Ketocholesterols - pharmacology</subject><subject>Lipid membranes</subject><subject>Lipids</subject><subject>Liver</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Membranes</subject><subject>Mitochondria</subject><subject>Mitochondria, Liver - drug effects</subject><subject>Mitochondria, Liver - metabolism</subject><subject>Niclosamide</subject><subject>Oxidative Coupling - drug effects</subject><subject>Oxidative phosphorylation</subject><subject>Oxidative Phosphorylation - drug effects</subject><subject>Phosphorylation</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Rats</subject><subject>Respiration</subject><subject>Uncoupling Agents - pharmacology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7jr6D0QLguhFxzRJv26EZfFjYGFBV2_DaT6mWTLJmLTDjv_J_2i6012mshcSStOT57zvSdKTJC9ztMxJlX-4doO3YJZbZ-USYUpp0zxKTvOG4KzEiDw-mp8kz0K4RqggdVk-TU4IIVVNc3qa_LnqZLrRveOds8JryHrwa9lLkQrp9Q56vZOpU2kfOW4gBM3BpIPlbtga6ccld6PFgdt2LsTH7038djbl4Ftn9yble7BaRKeMd8Z5t-1kDHd74eF3rD_VIQWbSqUkvxU6rsikXk5uz5MnCkyQL6b3Ivnx-dPV-dfs4vLL6vzsIuNlg_usKusoVZKGF6QAUUquOEiOVY1yXGJVFAqAUEQ4VHkRZzXlJMeCQN4WqhZkkbw-6G6NC2w66cAwrSimDSJVJFYHQji4ZluvN-D3zIFmtwHn1wx8r7mRDJUct4VoKhSdRB1ro7huSkrbFlMSg4vk4-Q2tBspuLS9BzMTna9Y3bG127GqqgiOY5G8mwS8-zXI0LONDlwaA1a64VA3baoG1RF98w_68O4mag1xA9oqF335KMrOSlqhOkdotF0-QMUh5EbzeK1Kx_gs4f0sITK9vOnXMITAVt-__T97-XPOvj1iOwmm74Izw_gPhjlIDyD3LgQv1f0h54iNXXV3GmzsKjZ1VUx7dXxB90l3bUT-ArdmIjA</recordid><startdate>20201230</startdate><enddate>20201230</enddate><creator>Iaubasarova, Iliuza R</creator><creator>Khailova, Ljudmila S</creator><creator>Firsov, Alexander M</creator><creator>Grivennikova, Vera G</creator><creator>Kirsanov, Roman S</creator><creator>Korshunova, Galina A</creator><creator>Kotova, Elena A</creator><creator>Antonenko, Yuri N</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0244-855X</orcidid></search><sort><creationdate>20201230</creationdate><title>The mitochondria-targeted derivative of the classical uncoupler of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone is an effective mitochondrial recoupler</title><author>Iaubasarova, Iliuza R ; Khailova, Ljudmila S ; Firsov, Alexander M ; Grivennikova, Vera G ; Kirsanov, Roman S ; Korshunova, Galina A ; Kotova, Elena A ; Antonenko, Yuri N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-768eff639c535ad6ecfcaec2f801262f55faa3403ca715a3484c312d3a1b5f8d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>2,4-Dinitrophenol</topic><topic>Animals</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Carbonyl compounds</topic><topic>Carbonyl Cyanide m-Chlorophenyl Hydrazone - analogs & derivatives</topic><topic>Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology</topic><topic>Carbonyls</topic><topic>Cattle</topic><topic>Cyanides</topic><topic>E coli</topic><topic>Ketocholesterols - pharmacology</topic><topic>Lipid membranes</topic><topic>Lipids</topic><topic>Liver</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - physiology</topic><topic>Membranes</topic><topic>Mitochondria</topic><topic>Mitochondria, Liver - drug effects</topic><topic>Mitochondria, Liver - metabolism</topic><topic>Niclosamide</topic><topic>Oxidative Coupling - drug effects</topic><topic>Oxidative phosphorylation</topic><topic>Oxidative Phosphorylation - drug effects</topic><topic>Phosphorylation</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Rats</topic><topic>Respiration</topic><topic>Uncoupling Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iaubasarova, Iliuza R</creatorcontrib><creatorcontrib>Khailova, Ljudmila S</creatorcontrib><creatorcontrib>Firsov, Alexander M</creatorcontrib><creatorcontrib>Grivennikova, Vera G</creatorcontrib><creatorcontrib>Kirsanov, Roman S</creatorcontrib><creatorcontrib>Korshunova, Galina A</creatorcontrib><creatorcontrib>Kotova, Elena A</creatorcontrib><creatorcontrib>Antonenko, Yuri N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Science (Gale in Context)</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals (DOAJ)</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iaubasarova, Iliuza R</au><au>Khailova, Ljudmila S</au><au>Firsov, Alexander M</au><au>Grivennikova, Vera G</au><au>Kirsanov, Roman S</au><au>Korshunova, Galina A</au><au>Kotova, Elena A</au><au>Antonenko, Yuri N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The mitochondria-targeted derivative of the classical uncoupler of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone is an effective mitochondrial recoupler</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-12-30</date><risdate>2020</risdate><volume>15</volume><issue>12</issue><spage>e0244499</spage><epage>e0244499</epage><pages>e0244499-e0244499</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The synthesis of a mitochondria-targeted derivative of the classical mitochondrial uncoupler carbonyl cyanide-m-chlorophenylhydrazone (CCCP) by alkoxy substitution of CCCP with n-decyl(triphenyl)phosphonium cation yielded mitoCCCP, which was able to inhibit the uncoupling action of CCCP, tyrphostin A9 and niclosamide on rat liver mitochondria, but not that of 2,4-dinitrophenol, at a concentration of 1-2 μM. MitoCCCP did not uncouple mitochondria by itself at these concentrations, although it exhibited uncoupling action at tens of micromolar concentrations. Thus, mitoCCCP appeared to be a more effective mitochondrial recoupler than 6-ketocholestanol. Both mitoCCCP and 6-ketocholestanol did not inhibit the protonophoric activity of CCCP in artificial bilayer lipid membranes, which might compromise the simple proton-shuttling mechanism of the uncoupling activity on mitochondria.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33378414</pmid><doi>10.1371/journal.pone.0244499</doi><tpages>e0244499</tpages><orcidid>https://orcid.org/0000-0002-0244-855X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-12, Vol.15 (12), p.e0244499-e0244499 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2474249037 |
| source | Directory of Open Access Journals (DOAJ); MEDLINE; Public Library of Science; PubMed Central; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | 2,4-Dinitrophenol Animals Biology Biology and Life Sciences Carbonyl compounds Carbonyl Cyanide m-Chlorophenyl Hydrazone - analogs & derivatives Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology Carbonyls Cattle Cyanides E coli Ketocholesterols - pharmacology Lipid membranes Lipids Liver Membrane Potentials - drug effects Membrane Potentials - physiology Membranes Mitochondria Mitochondria, Liver - drug effects Mitochondria, Liver - metabolism Niclosamide Oxidative Coupling - drug effects Oxidative phosphorylation Oxidative Phosphorylation - drug effects Phosphorylation Physical Sciences Physiological aspects Proteins Rats Respiration Uncoupling Agents - pharmacology |
| title | The mitochondria-targeted derivative of the classical uncoupler of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone is an effective mitochondrial recoupler |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T15%3A56%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20mitochondria-targeted%20derivative%20of%20the%20classical%20uncoupler%20of%20oxidative%20phosphorylation%20carbonyl%20cyanide%20m-chlorophenylhydrazone%20is%20an%20effective%20mitochondrial%20recoupler&rft.jtitle=PloS%20one&rft.au=Iaubasarova,%20Iliuza%20R&rft.date=2020-12-30&rft.volume=15&rft.issue=12&rft.spage=e0244499&rft.epage=e0244499&rft.pages=e0244499-e0244499&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0244499&rft_dat=%3Cgale_plos_%3EA647081002%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2474249037&rft_id=info:pmid/33378414&rft_galeid=A647081002&rft_doaj_id=oai_doaj_org_article_06c2b5d970a34d868e4289644bb2430a&rfr_iscdi=true |