{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:17:20Z","timestamp":1778577440420,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T00:00:00Z","timestamp":1570406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS098772"],"award-info":[{"award-number":["R01 NS098772"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008474","name":"New Jersey Commission on Brain Injury Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008474","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Although the mechanisms by which mutant huntingtin (mHtt) results in Huntington's disease (HD) remain unclear, mHtt\u2010induced mitochondrial defects were implicated in HD pathogenesis. The effect of mHtt could be mediated by transcriptional alterations, by direct interaction with mitochondria, or by both. In the present study, we tested a hypothesis that mHtt directly damages mitochondria. To test this hypothesis, we applied brain cytosolic fraction from YAC128 mice, containing mHtt, to brain non\u2010synaptic and synaptic mitochondria from wild\u2010type mice and assessed mitochondrial respiration with a Clark\u2010type oxygen electrode, membrane potential and Ca<jats:sup>2+<\/jats:sup> uptake capacity with tetraphenylphosphonium (TPP<jats:sup>+<\/jats:sup>)\u2010 and Ca<jats:sup>2+<\/jats:sup>\u2010sensitive electrodes, respectively, and, reactive oxygen species production with Amplex Red assay. The amount of mHtt bound to mitochondria following incubation with mHtt\u2010containing cytosolic fraction was greater than the amount of mHtt bound to brain mitochondria isolated from YAC128 mice. Despite mHtt binding to wild\u2010type mitochondria, no abnormalities in mitochondrial functions were detected. This is consistent with our previous results demonstrating the lack of defects in brain mitochondria isolated from R6\/2 and YAC128 mice. This, however, could be because of partial loss of mitochondrially bound mHtt during the isolation procedure. Consequently, we increased the amount of mitochondrially bound mHtt by incubating brain non\u2010synaptic and synaptic mitochondria isolated from YAC128 mice with mHtt\u2010containing cytosolic fraction. Despite the enrichment of YAC128 brain mitochondria with mHtt, mitochondrial functions (respiration, membrane potential, reactive oxygen species production, Ca<jats:sup>2+<\/jats:sup> uptake capacity) remained unchanged. Overall, our results suggest that mHtt does not directly impair mitochondrial functions, arguing against the involvement of this mechanism in HD pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\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\/jnc14852-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Open Science: This manuscript was awarded with the Open Materials Badge<\/jats:p><jats:p>For more information see: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/cos.io\/our-services\/open-science-badges\/\">https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14852","type":"journal-article","created":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T12:51:22Z","timestamp":1565959882000},"page":"716-731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mutant huntingtin fails to directly impair brain mitochondria"],"prefix":"10.1111","volume":"151","author":[{"given":"James","family":"Hamilton","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Brustovetsky","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-2560","authenticated-orcid":false,"given":"Nickolay","family":"Brustovetsky","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,7]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1","article-title":"Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6\/2 mouse model","volume":"5","author":"Aidt F. 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