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The pROS of Autophagy in Neuronal Health

Lookup NU author(s): Lucy Sedlackova, George Kelly, Dr Viktor Korolchuk

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2020 The AuthorsAutophagy refers to a set of catabolic pathways that together facilitate degradation of superfluous, damaged and toxic cellular components. The most studied type of autophagy, called macroautophagy, involves membrane mobilisation, cargo engulfment and trafficking of the newly formed autophagic vesicle to the recycling organelle, the lysosome. Macroautophagy responds to a variety of intra- and extra-cellular stress conditions including, but not limited to, pathogen intrusion, oxygen or nutrient starvation, proteotoxic and organelle stress, and elevation of reactive oxygen species (ROS). ROS are highly reactive oxygen molecules that can interact with cellular macromolecules (proteins, lipids, nucleic acids) to either modify their activity or, when released in excess, inflict irreversible damage. Although increased ROS release has long been recognised for its involvement in macroautophagy activation, the underlying mechanisms and the wider impact of ROS-mediated macroautophagy stimulation remain incompletely understood. We therefore discuss the growing body of evidence that describes the variety of mechanisms modulated by ROS that trigger cytoprotective detoxification via macroautophagy. We outline the role of ROS in signalling upstream of autophagy initiation, by increased gene expression and post-translational modifications of transcription factors, and in the formation and nucleation of autophagic vesicles by cysteine modification of conserved autophagy proteins including ATG4B, ATG7 and ATG3. Furthermore, we review the effect of ROS on selective forms of macroautophagy, specifically on cargo recognition by autophagy receptor proteins p62 and NBR1 (neighbour of BRCA1) and the recycling of mitochondria (mitophagy), and peroxisomes (pexophagy). Finally, we highlight both, the standalone and mutual contributions of abnormal ROS signalling and macroautophagy to the development and progression of neurodegenerative diseases.


Publication metadata

Author(s): Sedlackova L, Kelly G, Korolchuk VI

Publication type: Review

Publication status: Published

Journal: Journal of Molecular Biology

Year: 2020

Pages: epub ahead of print

Online publication date: 30/01/2020

Acceptance date: 10/01/2020

ISSN (print): 0022-2836

ISSN (electronic): 1089-8638

Publisher: Academic Press

URL: https://doi.org/10.1016/j.jmb.2020.01.020

DOI: 10.1016/j.jmb.2020.01.020

PubMed id: 32006535


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