Complex I and Complex III of Mitochondria Have Common Inhibitors Acting as Ubiquinone Antagonists
Mitochondrial complex I and complex III have common inhibitors with ubiquinone-like structure. The tridecyl analog of stigmatellin, which inhibits mitochondrial complex III at nanomolar concentrations, also inhibits the NADH: ubiquinone reductase activity of complex I at micromolar concentrations. T...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1993-02, Vol.190 (3), p.1090-1096 |
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| container_end_page | 1096 |
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| container_issue | 3 |
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| container_title | Biochemical and biophysical research communications |
| container_volume | 190 |
| creator | Esposti, M.D. Ghelli, A. Crimi, M. Estornell, E. Fato, R. Lenaz, G. |
| description | Mitochondrial complex I and complex III have common inhibitors with ubiquinone-like structure. The tridecyl analog of stigmatellin, which inhibits mitochondrial complex III at nanomolar concentrations, also inhibits the NADH: ubiquinone reductase activity of complex I at micromolar concentrations. The inhibitor titer depends upon the concentration of the mitochondrial particles and extrapolates to 0.2 μM at zero particle concentration. The stigmatellin analog is more powerful than its parent compound and is noncompetitive with exogenous ubiquinone, rotenone and piericidin.Myxothiazol, which is another potent inhibitor of complex III, is also found to inhibit the activity of complex I with a titer comparable to that of the tridecyl analog of stigmatellin. Additionally, piericidin, which is the most powerful inhibitor of complex I, inhibits the ubiquinol: cytochrome
c reductase activity of complex III at micromolar concentrations in mitochondrial particles and atsubmicromolar concentrations in the isolated enzyme complex. |
| doi_str_mv | 10.1006/bbrc.1993.1161 |
| format | Article |
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c reductase activity of complex III at micromolar concentrations in mitochondrial particles and atsubmicromolar concentrations in the isolated enzyme complex.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cattle</subject><subject>Electron Transport Complex I</subject><subject>Electron Transport Complex III - antagonists & inhibitors</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>In Vitro Techniques</subject><subject>NADH, NADPH Oxidoreductases - antagonists & inhibitors</subject><subject>Oxidation-Reduction</subject><subject>Oxidoreductases</subject><subject>Sheep</subject><subject>Submitochondrial Particles - metabolism</subject><subject>Ubiquinone - antagonists & inhibitors</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM9PwyAYhonR6Pxx9WbCwXjrhLbUclwWdU00XjTxRuArbJgWJnSL_vfSbNnNC4S8D2--70HompIpJaS6VyrAlHJeTCmt6BGaUMJJllNSHqMJSUSWc_p5hs5j_CKE0rLip-i0LgteED5Bcu77dad_cIOla_Hh1TTYG_xqBw8r79pgJV7IrR6B3jvcuJVVKQwRz2CwbollxB_Kfm-s807jmRvk0jsbh3iJTozsor7a3xfo4-nxfb7IXt6em_nsJYOiqocMKq6UMZDOmssCSm5y0K3O65anmTXJFSNQm4JLKh8AKskMVSZnvC4IsLy4QHe73nXw3xsdB9HbCLrrpNN-E8UDY7wkrErgdAdC8DEGbcQ62F6GX0GJGJ2K0akYnYrRafpws2_eqF63B3wvMeW3-1xGkJ0J0oGNB6xkNWV8rKl3mE4WtlYHEcFql5a0QcMgWm__m-APEf-TEA</recordid><startdate>19930215</startdate><enddate>19930215</enddate><creator>Esposti, M.D.</creator><creator>Ghelli, A.</creator><creator>Crimi, M.</creator><creator>Estornell, E.</creator><creator>Fato, R.</creator><creator>Lenaz, G.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</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>19930215</creationdate><title>Complex I and Complex III of Mitochondria Have Common Inhibitors Acting as Ubiquinone Antagonists</title><author>Esposti, M.D. ; Ghelli, A. ; Crimi, M. ; Estornell, E. ; Fato, R. ; Lenaz, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-c69bbffc9bb89a3c49f2cede28d9469e02b50c8f39a1a7cc6a5f1bf259830c523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cattle</topic><topic>Electron Transport Complex I</topic><topic>Electron Transport Complex III - antagonists & inhibitors</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>In Vitro Techniques</topic><topic>NADH, NADPH Oxidoreductases - antagonists & inhibitors</topic><topic>Oxidation-Reduction</topic><topic>Oxidoreductases</topic><topic>Sheep</topic><topic>Submitochondrial Particles - metabolism</topic><topic>Ubiquinone - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Esposti, M.D.</creatorcontrib><creatorcontrib>Ghelli, A.</creatorcontrib><creatorcontrib>Crimi, M.</creatorcontrib><creatorcontrib>Estornell, E.</creatorcontrib><creatorcontrib>Fato, R.</creatorcontrib><creatorcontrib>Lenaz, G.</creatorcontrib><collection>Pascal-Francis</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>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Esposti, M.D.</au><au>Ghelli, A.</au><au>Crimi, M.</au><au>Estornell, E.</au><au>Fato, R.</au><au>Lenaz, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complex I and Complex III of Mitochondria Have Common Inhibitors Acting as Ubiquinone Antagonists</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1993-02-15</date><risdate>1993</risdate><volume>190</volume><issue>3</issue><spage>1090</spage><epage>1096</epage><pages>1090-1096</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><coden>BBRCA9</coden><abstract>Mitochondrial complex I and complex III have common inhibitors with ubiquinone-like structure. The tridecyl analog of stigmatellin, which inhibits mitochondrial complex III at nanomolar concentrations, also inhibits the NADH: ubiquinone reductase activity of complex I at micromolar concentrations. The inhibitor titer depends upon the concentration of the mitochondrial particles and extrapolates to 0.2 μM at zero particle concentration. The stigmatellin analog is more powerful than its parent compound and is noncompetitive with exogenous ubiquinone, rotenone and piericidin.Myxothiazol, which is another potent inhibitor of complex III, is also found to inhibit the activity of complex I with a titer comparable to that of the tridecyl analog of stigmatellin. Additionally, piericidin, which is the most powerful inhibitor of complex I, inhibits the ubiquinol: cytochrome
c reductase activity of complex III at micromolar concentrations in mitochondrial particles and atsubmicromolar concentrations in the isolated enzyme complex.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>8439309</pmid><doi>10.1006/bbrc.1993.1161</doi><tpages>7</tpages></addata></record> |
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| subjects | Analytical, structural and metabolic biochemistry Animals Biological and medical sciences Cattle Electron Transport Complex I Electron Transport Complex III - antagonists & inhibitors Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology In Vitro Techniques NADH, NADPH Oxidoreductases - antagonists & inhibitors Oxidation-Reduction Oxidoreductases Sheep Submitochondrial Particles - metabolism Ubiquinone - antagonists & inhibitors |
| title | Complex I and Complex III of Mitochondria Have Common Inhibitors Acting as Ubiquinone Antagonists |
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