TY - JOUR
T1 - Autophagocytosis of mitochondria is prominent in Alzheimer disease
AU - Moreira, Paula I.
AU - Siedlak, Sandra L.
AU - Wang, Xinglong
AU - Santos, Maria S.
AU - Oliveira, Catarina R.
AU - Tabaton, Massimo
AU - Nunomura, Akihiko
AU - Szweda, Luke I.
AU - Aliev, Gjumrakch
AU - Smith, Mark A.
AU - Zhu, Xiongwei
AU - Perry, George
PY - 2007/6
Y1 - 2007/6
N2 - Mitochondrial abnormalities are prominent in Alzheimer disease. In this study, 2 mitochondrial markers, cytochrome oxidase-1 and lipoic acid, a sulfur-containing cofactor required for the activity of several mitochondrial enzyme complexes, were compared using light and electron microscopic analyses and immunoblot assays. Both lipoic acid and cytochrome oxidase-1 immunoreactivity are increased in the cytoplasm of pyramidal neurons in Alzheimer disease compared with control cases. Of significance, lipoic acid was found to be strongly associated with granular structures, and ultrastructure analysis showed localization to mitochondria, cytosol, and, importantly, in organelles identified as autophagic vacuoles and lipofuscin in Alzheimer disease but not control cases. Cytochrome oxidase-1 immunoreactivity was limited to mitochondria and cytosol in both Alzheimer and control cases. These data suggest that mitochondria are key targets of increased autophagic degradation in Alzheimer disease. Whether increased autophagocytosis is a consequence of an increased turnover of mitochondria or whether the mitochondria in Alzheimer disease are more susceptible to autophagy remains to be resolved.
AB - Mitochondrial abnormalities are prominent in Alzheimer disease. In this study, 2 mitochondrial markers, cytochrome oxidase-1 and lipoic acid, a sulfur-containing cofactor required for the activity of several mitochondrial enzyme complexes, were compared using light and electron microscopic analyses and immunoblot assays. Both lipoic acid and cytochrome oxidase-1 immunoreactivity are increased in the cytoplasm of pyramidal neurons in Alzheimer disease compared with control cases. Of significance, lipoic acid was found to be strongly associated with granular structures, and ultrastructure analysis showed localization to mitochondria, cytosol, and, importantly, in organelles identified as autophagic vacuoles and lipofuscin in Alzheimer disease but not control cases. Cytochrome oxidase-1 immunoreactivity was limited to mitochondria and cytosol in both Alzheimer and control cases. These data suggest that mitochondria are key targets of increased autophagic degradation in Alzheimer disease. Whether increased autophagocytosis is a consequence of an increased turnover of mitochondria or whether the mitochondria in Alzheimer disease are more susceptible to autophagy remains to be resolved.
KW - Cytochrome oxidase-1
KW - Immunoelectron microscopy
KW - Lipoic acid
KW - Proteolysis
KW - Pyruvate dehydrogenase
KW - Ultrastructure
KW - α-Ketoglutarate dehydrogenase
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U2 - 10.1097/01.jnen.0000240476.73532.b0
DO - 10.1097/01.jnen.0000240476.73532.b0
M3 - Article
C2 - 17549012
AN - SCOPUS:34249881080
SN - 0022-3069
VL - 66
SP - 525
EP - 532
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 6
ER -