Mitochondrial FOXO3a is involved in amyloid β peptide-induced mitochondrial dysfunction

Journal of Bioenergetics and Biomembranes
Chun ShiXiumei Luo

Abstract

Mitochondrial dysfunction is a hallmark of amyloid β peptide (Aβ)-induced neuronal toxicity in Alzheimer's disease (AD). However, the precise mechanism(s) of Aβ-induced mitochondrial dysfunction has not been fully understood. There is evidence that Forkhead box O3a (FOXO3a) is normally present in neuronal mitochondria. Using HT22 murine hippocampal neuronal cells and primary hippocampal neurons, the present study investigated whether mitochondrial FOXO3a was involved in mitochondrial dysfunction induced by Aβ. It was found that Aβ induced dephosphorylation and mitochondrial translocation of FOXO3a. In addition, Aβ enhanced association of FOXO3a with mitochondrial DNA (mtDNA), causing a decrease in the expression of cytochrome c oxidase subunit 1 (COX1) and the activity of COX. In addition, Aβ-induced mitochondrial dysfunction, indicated by the decrease in 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) conversion, mitochondrial adenosine triphosphate (ATP) production and COX activity, could be suppressed by knockdown of FOXO3a (FOXO3a-KD). These results provide new insights into the mechanism underlying Aβ-induced neurotoxicity and open up new therapeutic perspectives for AD.

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Citations

Oct 4, 2016·Molecular Neurobiology·Hao HuJin-Tai Yu
Mar 27, 2020·Frontiers in Cellular Neuroscience·Ndidi-Ese UzorAndrey S Tsvetkov
Sep 29, 2020·Neural Regeneration Research·Kenneth Maiese
Apr 30, 2020·Current Neuropharmacology·Ashish SharmaRohit Goyal
Dec 18, 2021·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Jennifer A MargrettBradley J Willcox

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