Oxidation of p62 as an evolutionary adaptation to promote autophagy in stress conditions
Authors:Elsje G. Otten1,§, Rhoda Stefanatos1, Bernadette Carroll1, Viktor I. Korolchuk1
1 Institute for Cell and Molecular Biosciences (ICaMB); Newcastle University Institute for Ageing (NUIA); Newcastle University; Campus for Ageing and Vitality; Newcastle upon Tyne, UK.
§ Current address: MRC Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Keywords:
Amyotrophic Lateral Sclerosis, reactive oxygen species.
Corresponding Author(s):
Conflict of interest statement:
Authors declare no conflict of interest.
Please cite this article as:
Elsje G. Otten, Rhoda Stefanatos, Bernadette Carroll, Viktor I. Korolchuk (2018). Oxidation of p62 as an evolutionary adaptation to promote autophagy in stress conditions. Cell Stress 2(4): 91-93. doi: 10.15698/cst2018.04.132
© 2018 Otten et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Ageing and age-related diseases are characterised by increased oxidative and proteotoxic stress, which results in negative effects on cell function and survival. The cell possesses several mechanisms to deal with damaged proteins, including degradation via macroautophagy (hereafter called autophagy). This essential cellular pathway is conserved from yeast to humans and it is well established that its impairment reduces lifespan in multiple model organisms, including worms, flies and mice. In our study, recently published in Nature Communications, we asked if longer lifespan characteristic of higher organisms is the result of evolutionary adaptations to the autophagy machinery. We found that the autophagy receptor p62 can be oxidised leading to its oligomerisation which ultimately promotes autophagy. However this mechanism, present in vertebrates, has been acquired late in evolution. We propose that the ability of p62 to sense reactive oxygen species (ROS) via oxidation, and potentially other similar modifications, may have evolved in higher organisms and contributed to their increased lifespan. Indeed, impairment of this process could result in age-related neurodegeneration in humans.