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Mitochondrial Autophagocytosis in Alzheimer Disease
Author(s) -
Perry George,
Moreira Paula I.,
Siedlak Sandra L.,
Santos Maria S.,
Oliveira Catarina R.,
Fujioka Hisashi,
Tabaton Massimo,
Nunomura Akihiko,
Aliev Gjumrakch,
Szweda Luke I.,
Smith Mark A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a73-c
Subject(s) - mitochondrion , lipofuscin , cytosol , cytochrome c oxidase , autophagy , organelle , lipoic acid , vacuole , alzheimer's disease , biology , cytoplasm , pathology , disease , biochemistry , medicine , enzyme , antioxidant , apoptosis
Mitochondrial abnormalities are prominent in Alzheimer disease. In this study, we compared localization of two mitochondrial markers and observed that cases of Alzheimer disease presented both increased lipoic acid and cytochrome oxidase‐1 immunoreactivity in the cytoplasm when compared with age‐matched and young controls. However, immunoblots showed that cases of Alzheimer disease present lower lipoic acid content, ~75 and ~50 kDa, when compared with young and age‐matched controls. This paradox of increased immunoreactivity and reduced proteins was illuminated by ultrastructure analysis that showed lipoic acid immunodecoration was not only localized to mitochondria and cytosol but also in organelles identified as autophagic vacuoles and lipofuscin in samples from cases of Alzheimer disease but not controls. In contrast, cytochrome oxidase‐1 immunoreactivity was limited to mitochondria and cytosol. These results indicate that mitochondria are key targets of increased autophagic degradation in Alzheimer disease. Work in the authors' laboratories is supported by the Alzheimer's Association, Philip Morris USA Inc. and Philip Morris International.