| Autor: |
Walls KC; Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4545, USA. kwalls@uci.edu, Coskun P, Gallegos-Perez JL, Zadourian N, Freude K, Rasool S, Blurton-Jones M, Green KN, LaFerla FM |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2012 Aug 31; Vol. 287 (36), pp. 30317-27. Date of Electronic Publication: 2012 Jun 29. |
| DOI: |
10.1074/jbc.M112.365890 |
| Abstrakt: |
Alzheimer disease (AD) is a complex disorder that involves numerous cellular and subcellular alterations including impairments in mitochondrial homeostasis. To better understand the role of mitochondrial dysfunction in the pathogenesis of AD, we analyzed brains from clinically well-characterized human subjects and from the 3xTg-AD mouse model of AD. We find Aβ and critical components of the γ-secretase complex, presenilin-1, -2, and nicastrin, accumulate in the mitochondria. We used a proteomics approach to identify binding partners and show that heat shock protein 60 (HSP60), a molecular chaperone localized to mitochondria and the plasma membrane, specifically associates with APP. We next generated stable neural cell lines expressing human wild-type or Swedish APP, and provide corroborating in vitro evidence that HSP60 mediates translocation of APP to the mitochondria. Viral-mediated shRNA knockdown of HSP60 attenuates APP and Aβ mislocalization to the mitochondria. Our findings identify a novel interaction between APP and HSP60, which accounts for its translocation to the mitochondria. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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