{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T13:07:41Z","timestamp":1776172061408,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,6,25]],"date-time":"2002-06-25T00:00:00Z","timestamp":1024963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Examination of the downstream mediators responsible for inhibition of mitochondrial respiration by dopamine (DA) was investigated. Consistent with findings reported by others, exposure of rat brain mitochondria to 0.5\u2003m<jats:sc>m<\/jats:sc> DA for 15\u2003min at 30\u00b0C inhibited pyruvate\/glutamate\/malate\u2010supported state\u20103 respiration by 20%. Inhibition was prevented in the presence of pargyline and clorgyline demonstrating that mitochondrial inhibition arose from products formed following MAO metabolism and could include hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>), hydroxyl radical, oxidized glutathione (GSSG) or glutathione\u2013protein mixed disulfides (PrSSG). As with DA, direct incubation of intact mitochondria with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> (100\u2003\u00b5<jats:sc>m<\/jats:sc>) significantly inhibited state\u20103 respiration. In contrast, incubation with GSSG (1\u2003m<jats:sc>m<\/jats:sc>) had no effect on O<jats:sub>2<\/jats:sub> consumption. Exposure of mitochondria to 1\u2003m<jats:sc>m<\/jats:sc> GSSG resulted in a 3.3\u2010fold increase in PrSSG formation compared with 1.4\u2010 and 1.5\u2010fold increases in the presence of 100\u2003\u00b5<jats:sc>m<\/jats:sc> H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> or 0.5\u2003m<jats:sc>m<\/jats:sc> DA, respectively, suggesting a dissociation between PrSSG formation and effects on respiration. The lack of inhibition of respiration by GSSG could not be accounted for by inadequate delivery of GSSG into mitochondria as increases in PrSSG levels in both membrane\u2010bound (2\u2010fold) and intramatrix (3.5\u2010fold) protein compartments were observed. Furthermore, GSSG was without effect on electron transport chain activities in freeze\u2013thawed brain mitochondria or in pig heart electron transport particles (ETP). In contrast, H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> showed differential effects on inhibition of respiration supported by different substrates with a sensitivity of succinate &gt; pyruvate\/malate &gt; glutamate\/malate. NADH oxidase and succinate oxidase activities in freeze\u2013thawed mitochondria were inhibited with IC<jats:sub>50<\/jats:sub> approximately 2\u20133\u2010fold higher than in intact mitochondria. ETPs, however, were relatively insensitive to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. Co\u2010administration of desferrioxamine with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> had no effect on complex I\u2010associated inhibition in intact mitochondria, but attenuated inhibition of rotenone\u2010sensitive NADH oxidase activity by 70% in freeze\u2013thawed mitochondria. The results show that DA\u2010associated inhibition of respiration is dependent on MAO and that H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and its downstream hydroxyl radical rather than increased GSSG and subsequent PrSSG formation mediate the effects.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2002.00938.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T07:01:30Z","timestamp":1047452490000},"page":"66-74","source":"Crossref","is-referenced-by-count":54,"title":["Inhibition of brain mitochondrial respiration by dopamine: involvement of H<sub>2<\/sub>O<sub>2<\/sub> and hydroxyl radicals but not glutathione\u2013protein\u2013mixed disulfides"],"prefix":"10.1111","volume":"82","author":[{"given":"Martin","family":"Gluck","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Ehrhart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Jayatilleke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail D.","family":"Zeevalk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,6,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(78)90670-8"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90087-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/1357-2725(95)00019-L"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64020718.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0731127.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/81834"},{"key":"e_1_2_7_8_1","first-page":"95","article-title":"Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy","volume":"125","author":"Blin O.","year":"1994","journal-title":"J. Neurosci."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(82)90393-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(83)90014-X"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.14.4546"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1979.59.3.527"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"4724","DOI":"10.1016\/S0021-9258(18)62854-6","article-title":"Metabolism of rat brain mitochondria: preparation and characterization","volume":"245","author":"Clark J. B.","year":"1970","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0732310.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.10.4890"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(79)90006-4"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00355.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)33682-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1016\/S0021-9258(17)41844-8","article-title":"Characterization of the inhibitory mechanism of 1\u2010methyl\u20104\u2010phenylpyridinium and 4\u2010phenylpyridine analogs in inner membrane preparations","volume":"269","author":"Gluck M. R.","year":"1994","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00064a021"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(80)90139-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00815a016"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1989.tb01779.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1996.0510"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6610213"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5494.1068a"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420520405"},{"key":"e_1_2_7_28_1","first-page":"19","article-title":"Biochemical pathophysiology of Parkinson's disease","volume":"45","author":"Hornykiewicz O.","year":"1986","journal-title":"Adv. Neurol."},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00484-1"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01277665"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6823561"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)91141-8"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66031174.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(88)90038-4"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410260606"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410340515"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.2000.0836"},{"key":"e_1_2_7_39_1","first-page":"79","volume-title":"Mitochondria: A Practical Approach","author":"Ragan C. I.","year":"1987"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)92004-J"},{"key":"e_1_2_7_41_1","first-page":"G247","article-title":"Oxidative stress induces S\u2010thiolation of specific proteins in cultured gastric mucosal cells","volume":"29","author":"Rokutan K.","year":"1994","journal-title":"Am. J. Physiol."},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)92366-0"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb02325.x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.4049\/jimmunol.156.5.1973","article-title":"Protein S\u2010thiolation and dethiolation during the respiratory burst in human monocytes","volume":"156","author":"Seres T.","year":"1996","journal-title":"J. Immunol."},{"key":"e_1_2_7_45_1","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S0022-3565(25)10589-2","article-title":"Glutathione and protein thiol homeostasis in brain during reperfusion after cerebral ischemia","volume":"274","author":"Shivakumar B. R.","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00049-8"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1980.tb11222.x"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.4.1398"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400417"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1996.0560"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)46227-2"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.54.070185.001513"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1471-4159.2002.00938.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1471-4159.2002.00938.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T21:19:40Z","timestamp":1744492780000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1471-4159.2002.00938.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,6,25]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,7]]}},"alternative-id":["10.1046\/j.1471-4159.2002.00938.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1471-4159.2002.00938.x","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,6,25]]}}}