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

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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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Acknowledgments

We are grateful for the support from National Natural Science Foundation of China (No.81370395 and No.31160221), and Guangdong Natural Science Foundation (No. 2013010014468).

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Authors and Affiliations

  1. Department of Anatomy, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China

    Chun Shi, Shuilong Leng, Dahong Long & Xiumei Luo

  2. Department of Human Anatomy, Dali University, Dali, Yunnan, 671003, China

    Jianhua Zhu

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  1. Chun Shi
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  2. Jianhua Zhu
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  3. Shuilong Leng
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  4. Dahong Long
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  5. Xiumei Luo
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Correspondence to Xiumei Luo.

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Chun Shi and Jianhua Zhu these two authors contribute to this work equally

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Shi, C., Zhu, J., Leng, S. et al. Mitochondrial FOXO3a is involved in amyloid β peptide-induced mitochondrial dysfunction. J Bioenerg Biomembr 48, 189–196 (2016). https://doi.org/10.1007/s10863-016-9645-0

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  • DOI: https://doi.org/10.1007/s10863-016-9645-0

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