Expression of the alternative oxidase mitigates beta-amyloid production and toxicity in model systems

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http://hdl.handle.net/10138/224236

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El-Khoury , R , Kaulio , E , Lassila , K A , Crowther , D C , Jacobs , H T & Rustin , P 2016 , ' Expression of the alternative oxidase mitigates beta-amyloid production and toxicity in model systems ' , Free Radical Biology & Medicine , vol. 96 , pp. 57-66 . https://doi.org/10.1016/j.freeradbiomed.2016.04.006

Title: Expression of the alternative oxidase mitigates beta-amyloid production and toxicity in model systems
Author: El-Khoury, Riyad; Kaulio, Eveliina; Lassila, Katariina A.; Crowther, Damian C.; Jacobs, Howard T.; Rustin, Pierre
Contributor: University of Helsinki, Institute of Biotechnology
Date: 2016-07
Language: eng
Number of pages: 10
Belongs to series: Free Radical Biology & Medicine
ISSN: 0891-5849
URI: http://hdl.handle.net/10138/224236
Abstract: Mitochondrial dysfunction has been widely associated with the pathology of Alzheimer's disease, but there is no consensus on whether it is a cause or consequence of disease, nor on the precise mechanism(s). We addressed these issues by testing the effects of expressing the alternative oxidase AOX from Ciona intestinalis, in different models of AD pathology. AOX can restore respiratory electron flow when the cytochrome segment of the mitochondrial respiratory chain is inhibited, supporting ATP synthesis, maintaining cellular redox homeostasis and mitigating excess superoxide production at respiratory complexes I and III. In human HEK293-derived cells, AOX expression decreased the production of beta-amyloid peptide resulting from antimycin inhibition of respiratory complex III. Because hydrogen peroxide was neither a direct product nor substrate of AOX, the ability of AOX to mimic antioxidants in this assay must be indirect. In addition, AOX expression was able to partially alleviate the short lifespan of Drosophila models neuronally expressing human beta-amyloid peptides, whilst abrogating the induction of markers of oxidative stress. Our findings support the idea of respiratory chain dysfunction and excess ROS production as both an early step and as a pathologically meaningful target in Alzheimer's disease pathogenesis, supporting the concept of a mitochondrial vicious cycle underlying the disease. (C) 2016 The Authors. Published by Elsevier Inc.
Subject: Mitochondria
Neurodegeneration
Oxidative stress
Dementia
Alzheimer's disease
HIGHER-PLANT MITOCHONDRIA
CYTOCHROME-C-OXIDASE
ALZHEIMERS-DISEASE
OXIDATIVE STRESS
LIFE-SPAN
ENDOPLASMIC-RETICULUM
NADH DEHYDROGENASE
DROSOPHILA-MELANOGASTER
PRECURSOR PROTEIN
GENE-EXPRESSION
3111 Biomedicine
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