{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:54:38Z","timestamp":1791431678082,"version":"4.3.3"},"reference-count":81,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT2022\u201000227"],"award-info":[{"award-number":["PICT2022\u201000227"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT2019\u20100656"],"award-info":[{"award-number":["PICT2019\u20100656"]}],"id":[{"id":"10.13039\/501100006668","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":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mitochondrial respiratory complexes are organized into supercomplexes (SC) to regulate electron flow and mitigate oxidative stress. Alterations in SC organization in the brain may affect energy expenditure, oxidative stress, and neuronal survival. In this report, we investigated the amount, activity and organization of mitochondrial complex I (CI) in the hippocampus of 12\u2010month\u2010old McGill\u2010R\u2010Thy1\u2010APP transgenic (Tg) rats, an animal model of Alzheimer's\u2010like cerebral amyloidosis. By means of BN\u2010PAGE, we found that the organization of SC did not differ between genotypes, but a lower abundance of SC was detected in Tg compared to wild\u2010type (WT) rats. Using a more sensitive technique (2\u2010D electrophoresis followed by Western blot), higher levels of free CI and a decrease in the relative abundance of assembled CI in SC (I\u2010III\n                    <jats:sub>2<\/jats:sub>\n                    and I\u2010III\n                    <jats:sub>2<\/jats:sub>\n                    \u2010IV) were observed in Tg rats. In\u2010gel activity assays showed that the total activity of CI (CI\u2009+\u2009SC\u2010CI) is lower in Tg compared to WT, while Tg samples show a significant decrease in SC\u2010CI\u2010associated activity. This alteration in CI assembly was associated with nitro\u2010oxidative stress and changes in mitochondrial fusion\u2010fission parameters. To assess CI composition, we applied LC\u2013MS\/MS to the isolated CI from BN\u2010PAGE and found that 11 of 45 subunits described in mammals were found to be less abundant in Tg. We examined the levels of the nuclear\u2010derived NDUFA9 subunit, which is critical for CI assembly, and found higher levels in the cytoplasmic fraction and lower levels in the mitochondrial fraction in Tg, suggesting that brain amyloidosis affects the import of CI subunits from the cytosol to the mitochondria, destabilizing the SC. This is the first report to characterize the types, abundance and activity of SC in the hippocampus of an animal model of cerebral amyloidosis, providing additional experimental evidence for the molecular mechanisms underlying the brain bioenergetic deficit characteristic of Alzheimer's disease.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70017-fig-0010-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70017","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T23:29:41Z","timestamp":1739489381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Supramolecular Architecture of Mitochondrial Complex I in the Rat Brain Is Altered by Alzheimer's\u2010Like Cerebral Amyloidosis"],"prefix":"10.1111","volume":"169","author":[{"given":"Gisela V.","family":"Novack","sequence":"first","affiliation":[{"name":"Laboratory of Brain Aging and Neurodegeneration Fundaci\u00f3n Instituto Leloir, IIBBA\u2010CONICET  Buenos Ares Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4491-2039","authenticated-orcid":false,"given":"Pablo","family":"Galeano","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Aging and Neurodegeneration Fundaci\u00f3n Instituto Leloir, IIBBA\u2010CONICET  Buenos Ares Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas A.","family":"Defelipe","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Campanelli","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Aging and Neurodegeneration Fundaci\u00f3n Instituto Leloir, IIBBA\u2010CONICET  Buenos Ares Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S.","family":"Campuzano","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Aging and Neurodegeneration Fundaci\u00f3n Instituto Leloir, IIBBA\u2010CONICET  Buenos Ares Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Rotondaro","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Aging and Neurodegeneration Fundaci\u00f3n Instituto Leloir, IIBBA\u2010CONICET  Buenos Ares Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo M.","family":"Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Aging and Neurodegeneration Fundaci\u00f3n Instituto Leloir, IIBBA\u2010CONICET  Buenos Ares Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Do Carmo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2143-2745","authenticated-orcid":false,"given":"A. Claudio","family":"Cuello","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda M.","family":"Garc\u00eda\u2010Alai","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5759-1807","authenticated-orcid":false,"given":"Laura","family":"Morelli","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Aging and Neurodegeneration Fundaci\u00f3n Instituto Leloir, IIBBA\u2010CONICET  Buenos Ares Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2013.12.009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.01.012"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010019\u20100430\u2010y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020783614031"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319247110"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061582"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2021.03.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166798"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413855111"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2010.01.003"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24662"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1880031"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2010.516254"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034929"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3833"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1511"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.1067296"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522\u2010009\u20109254\u2010y"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-819621-2.00004-8"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.11.030"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.10.016"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010017\u20100580\u20109"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010024\u201003184\u20107"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.05.028"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12835"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010024\u201006552\u20104"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107541"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2010.02.003"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.10.028"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242317009"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00321"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2013.11.002"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2009.08.002"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19359"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806192105"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470942390.mo150182"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4814783"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024\u20103205(01)01074\u20108"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000661"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.258399"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.01.022"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006320"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00074\u201007"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000235853.70092.ba"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102010\u20101349"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3460"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1613701113"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010017\u20102191\u20102"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.09.078"},{"key":"e_1_2_10_51_1","doi-asserted-by":"crossref","unstructured":"Maharjan B.2018.\u201cQuantitative Western Blot Analysis With Replicate Samples.\u201dhttps:\/\/doi.org\/10.17504\/protocols.io.k6sczee.","DOI":"10.17504\/protocols.io.k6sczee"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl066"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x15615132"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4845"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201043865\u20100"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.335"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2011.08.010"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.10.006"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.1994.63062179.x"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.01.015"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102012\u2010120787"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2023.09.010"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.10.021"},{"key":"e_1_2_10_64_1","first-page":"100","volume-title":"Peroxynitrite: A Mediator of Nitric Oxide\u2010Dependent Mitochondrial Dysfunction in Pathology","author":"Quijano C.","year":"2006"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13205\u2010022\u201003123\u20104"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102010\u2010100504"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr0504440"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513525200"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12020221"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C112.436766"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19754"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102010\u2010100339"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2010.08.009"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.11.003"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010023\u201000654\u2010z"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13686"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205015666180904154446"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.62"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201020942\u2010w"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150181131"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001484\u20107"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19095"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T18:22:31Z","timestamp":1761070951000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.70017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":81,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/jnc.70017"],"URL":"https:\/\/doi.org\/10.1111\/jnc.70017","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70017"}}