{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:19:22Z","timestamp":1789690762543,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T00:00:00Z","timestamp":1433376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NINDS","award":["R01 NS078008"],"award-info":[{"award-number":["R01 NS078008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated Ca<jats:sup>2+<\/jats:sup> handling in isolated brain synaptic and non\u2010synaptic mitochondria and in cultured striatal neurons from the <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mouse model of Huntington's disease. Both synaptic and non\u2010synaptic mitochondria from 2\u2010 and 12\u2010month\u2010old <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice had larger Ca<jats:sup>2+<\/jats:sup> uptake capacity than mitochondria from <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>18 and wild\u2010type <jats:styled-content style=\"fixed-case\">FVB<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NJ<\/jats:styled-content> mice. Synaptic mitochondria from 12\u2010month\u2010old <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice had further augmented Ca<jats:sup>2+<\/jats:sup> capacity compared with mitochondria from 2\u2010month\u2010old <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice and age\u2010matched <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>18 and <jats:styled-content style=\"fixed-case\">FVB<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NJ<\/jats:styled-content> mice. This increase in Ca<jats:sup>2+<\/jats:sup> uptake capacity correlated with an increase in the amount of mutant huntingtin protein (mHtt) associated with mitochondria from 12\u2010month\u2010old <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice. We speculate that this may happen because of mHtt\u2010mediated sequestration of free fatty acids thereby increasing resistance of mitochondria to Ca<jats:sup>2+<\/jats:sup>\u2010induced damage. In experiments with striatal neurons from <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 and <jats:styled-content style=\"fixed-case\">FVB<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NJ<\/jats:styled-content> mice, brief exposure to 25 or 100\u00a0\u03bcM glutamate produced transient elevations in cytosolic Ca<jats:sup>2+<\/jats:sup> followed by recovery to near resting levels. Following recovery of cytosolic Ca<jats:sup>2+<\/jats:sup>, mitochondrial depolarization with <jats:styled-content style=\"fixed-case\">FCCP<\/jats:styled-content> produced comparable elevations in cytosolic Ca<jats:sup>2+<\/jats:sup>, suggesting similar Ca<jats:sup>2+<\/jats:sup> release and, consequently, Ca<jats:sup>2+<\/jats:sup> loads in neuronal mitochondria from <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 and <jats:styled-content style=\"fixed-case\">FVB<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NJ<\/jats:styled-content> mice. Together, our data argue against a detrimental effect of <jats:styled-content style=\"fixed-case\">mH<\/jats:styled-content>tt on Ca<jats:sup>2+<\/jats:sup> handling in brain mitochondria of <jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13165-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>We demonstrate that mutant huntingtin (mHtt) binds to brain synaptic and nonsynaptic mitochondria and the amount of mitochondria\u2010bound mHtt correlates with increased mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake capacity. We propose that this may happen due to mHtt\u2010mediated sequestration of free fatty acids thereby increasing resistance of mitochondria to Ca<jats:sup>2+<\/jats:sup>\u2010induced damage.<\/jats:p>","DOI":"10.1111\/jnc.13165","type":"journal-article","created":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T09:29:24Z","timestamp":1431422964000},"page":"652-667","source":"Crossref","is-referenced-by-count":48,"title":["Ca<sup>2+<\/sup> handling in isolated brain mitochondria and cultured neurons derived from the <scp>YAC<\/scp>128 mouse model of Huntington's disease"],"prefix":"10.1111","volume":"134","author":[{"given":"Jessica J.","family":"Pellman","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Brustovetsky","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nickolay","family":"Brustovetsky","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Stark Neuroscience Research Institute Indiana University School of Medicine Indianapolis, Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.9.3767"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03434"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10234"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.4.1127"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.08.035"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-01-00103.2000"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-22-08229.2000"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-3042.2001.00671.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-12-04858.2003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03036.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212661200"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.12.007"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh162"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10230"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20336"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-02-00623.1993"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.06.022"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3455-07.2007"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709555200"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20754"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1054\/plef.2002.0400"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.12.1875"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80764-3"},{"key":"e_1_2_7_26_1","doi-asserted-by":"crossref","first-page":"5409","DOI":"10.1523\/JNEUROSCI.19-13-05409.1999","article-title":"Expression of the striatal DARPP\u201032\/ARPP\u201021 phenotype in GABAergic neurons requires neurotrophins in\u00a0vivo and in\u00a0vitro","volume":"19","author":"Ivkovic S.","year":"1999","journal-title":"J. Neurosci."},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5687-08.2009"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01868720"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)01159-9"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01073-4"},{"key":"e_1_2_7_31_1","volume-title":"Principles of Biochemistry","author":"Lehninger A. L.","year":"1993"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2009.07.012"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704704200"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00276-X"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.09.018"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603845200"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.142448"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04361.x"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0106-08.2008"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-09-03019.1996"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn884"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9861(02)00585-4"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq247"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-45"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.04.007"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505294102"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.02.006"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702134200"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr308"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg169"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)36723-7"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903546106"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00366-0"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi407"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0590-05.2005"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00548.x"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.407726"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02127-X"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.03.010"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(95)00003-A"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.13165","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.13165","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.13165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T05:27:16Z","timestamp":1696224436000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.13165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,4]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1111\/jnc.13165"],"URL":"https:\/\/doi.org\/10.1111\/jnc.13165","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,4]]}}}