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Monoamine oxidase-A promotes protective autophagy in human SH-SY5Y neuroblastoma cells through Bcl-2 phosphorylation


Aslihan Ugun-Klusek

Theodosis S. Theodosi

Julia C. Fitzgerald


Christoph Ufer

David J. Boocock

Patrick Yu-Wai-Man

Lynn Bedford

E. Ellen Billett


Monoamine oxidases (MAOs) are located on the outer mitochondrial membrane and are drug targets for the treatment of neurological disorders. MAOs control the levels of neurotransmitters in the brain via oxidative deamination and contribute to reactive oxygen species (ROS) generation through their catalytic by-product H2O2. Increased ROS levels may modulate mitochondrial function and mitochondrial dysfunction is implicated in a vast array of disorders. However, the downstream effects of MAO-A mediated ROS production in a neuronal model has not been previously investigated.

In this study, using MAO-A overexpressing neuroblastoma cells, we demonstrate that higher levels of MAO-A protein/activity results in increased basal ROS levels with associated increase in protein oxidation. Increased MAO-A levels result in increased Lysine-63 linked ubiquitination of mitochondrial proteins and promotes autophagy through Bcl-2 phosphorylation. Furthermore, ROS generated locally on the mitochondrial outer membrane by MAO-A promotes phosphorylation of dynamin-1-like protein, leading to mitochondrial fragmentation and clearance without complete loss of mitochondrial membrane potential. Cellular ATP levels are maintained following MAO-A overexpression and complex IV activity/protein levels increased, revealing a close relationship between MAO-A levels and mitochondrial function. Finally, the downstream effects of increased MAO-A levels are dependent on the availability of amine substrates and in the presence of exogenous substrate, cell viability is dramatically reduced.

This study shows for the first time that MAO-A generated ROS is involved in quality control signalling, and increase in MAO-A protein levels leads to a protective cellular response in order to mediate removal of damaged macromolecules/organelles, but substrate availability may ultimately determine cell fate. The latter is particularly important in conditions such as Parkinson's disease, where a dopamine precursor is used to treat disease symptoms and highlights that the fate of MAO-A containing dopaminergic neurons may depend on both MAO-A levels and catecholamine substrate availability.


Ugun-Klusek, A., Theodosi, T. S., Fitzgerald, J. C., Burté, F., Ufer, C., Boocock, D. J., …Billett, E. E. (2019). Monoamine oxidase-A promotes protective autophagy in human SH-SY5Y neuroblastoma cells through Bcl-2 phosphorylation. Redox Biology, 20, 167-181.

Journal Article Type Article
Acceptance Date Oct 6, 2018
Online Publication Date Oct 9, 2018
Publication Date 2019-01
Deposit Date Mar 7, 2019
Publicly Available Date Mar 7, 2019
Journal Redox Biology
Print ISSN 2213-2317
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 20
Pages 167-181
Keywords Organic Chemistry; Biochemistry
Public URL
Additional Information This article is maintained by: Elsevier; Article Title: Monoamine oxidase-A promotes protective autophagy in human SH-SY5Y neuroblastoma cells through Bcl-2 phosphorylation; Journal Title: Redox Biology; CrossRef DOI link to publisher maintained version:; Content Type: article; Copyright: © 2018 The Authors. Published by Elsevier B.V.


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