{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:19:29Z","timestamp":1791980369453,"version":"4.4.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,9,2]]},"abstract":"<jats:p>\n                    The amyloid \u03b2-peptide (A\u03b2) has been suggested to exert its toxicity intracellularly. Mitochondrial functions can be negatively affected by A\u03b2 and accumulation of A\u03b2 has been detected in mitochondria. Because A\u03b2 is not likely to be produced locally in mitochondria, we decided to investigate the mechanisms for mitochondrial A\u03b2 uptake. Our results from rat mitochondria show that A\u03b2 is transported into mitochondria via the translocase of the outer membrane (TOM) machinery. The import was insensitive to valinomycin, indicating that it is independent of the mitochondrial membrane potential. Subfractionation studies following the import experiments revealed A\u03b2 association with the inner membrane fraction, and immunoelectron microscopy after import showed localization of A\u03b2 to mitochondrial cristae. A similar distribution pattern of A\u03b2 in mitochondria was shown by immunoelectron microscopy in human cortical brain biopsies obtained from living subjects with normal pressure hydrocephalus. Thus, we present a unique import mechanism for A\u03b2 in mitochondria and demonstrate both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    that A\u03b2 is located to the mitochondrial cristae. Importantly, we also show that extracellulary applied A\u03b2 can be internalized by human neuroblastoma cells and can colocalize with mitochondrial markers. Together, these results provide further insight into the mitochondrial uptake of A\u03b2, a peptide considered to be of major significance in Alzheimer's disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0806192105","type":"journal-article","created":{"date-parts":[[2008,8,29]],"date-time":"2008-08-29T20:56:00Z","timestamp":1220043360000},"page":"13145-13150","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":618,"title":["The amyloid \u03b2-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae"],"prefix":"10.1073","volume":"105","author":[{"given":"Camilla A.","family":"Hansson Petersen","sequence":"first","affiliation":[{"name":"*Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center, NVS, Novum, 141 57 Huddinge, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyosha","family":"Alikhani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homira","family":"Behbahani","sequence":"additional","affiliation":[{"name":"*Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center, NVS, Novum, 141 57 Huddinge, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta","family":"Wiehager","sequence":"additional","affiliation":[{"name":"*Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center, NVS, Novum, 141 57 Huddinge, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel F.","family":"Pavlov","sequence":"additional","affiliation":[{"name":"*Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center, NVS, Novum, 141 57 Huddinge, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Alafuzoff","sequence":"additional","affiliation":[{"name":"Kuopio University Hospital, Institute of Clinical Medicine, Unit of Neurology\/Department of Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ville","family":"Leinonen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 70211 Kuopio, Finland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ito","sequence":"additional","affiliation":[{"name":"Dainippon Sumitomo Pharma Company Ltd., 564-0053 Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Winblad","sequence":"additional","affiliation":[{"name":"*Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center, NVS, Novum, 141 57 Huddinge, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Glaser","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ankarcrona","sequence":"additional","affiliation":[{"name":"*Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center, NVS, Novum, 141 57 Huddinge, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,9,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5440.735"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1037392100"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)91209-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.12.4245"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi060331"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001048s"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6448"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/416535a"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5167-03.2004"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64700-1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02737.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.09.007"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-3735fje"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-09-03017.2001"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-005-1762-7"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20474"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.40.8.1302"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.45.3.482"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02438.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb09439.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4276-04.2005"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1091230"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602532200"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200207030"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1469-06.2006"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.052705.163409"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)01440-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-007-0723-y"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl066"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04907.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00239-2"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.07.003"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.05.022"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701823200"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02026.x"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.57.2.551"},{"key":"e_1_3_3_37_2","volume-title":"Immunocytochemistry: Modern Methods and Applications","author":"Van Noorden S","year":"1986","unstructured":"S Van Noorden, Tissue preparation and immunostaining techniques for light microscopy. 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