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. 2013 Mar 22;288(18):12920–12931. doi: 10.1074/jbc.M112.424820

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© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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FIGURE 8. — Schematic representation of the effect of mitochondrial biogenesis on hIDE transcriptional activation and mitochondrial functionality. Activation of PGC1-α by the effect of mitochondrial biogenesis stimuli promotes NRF-1 expression, which impacts proximal hIDE-specific DNA binding domains, promoting the transcription of L-IDE and short IDE (S-IDE) mRNAs, which further translate the long (IDE-Met¹) and the short (IDE-Met⁴²) IDE isoforms. Mitochondrial Aβ can be degraded by IDE-Met¹-originating non-toxic peptides, or it can interact with cyclophilin D (CypD), Aβ-binding alcohol dehydrogenase (ABAD), or cytochrome c oxidase (COX), causing elevated reactive oxygen species (ROS). The balance between both processes results in functional or dysfunctional mitochondria, respectively.