Gundogdu, M., Tadayon, R., Salzano, G. , Shaw, G. S. and Walden, H. (2021) A mechanistic review of Parkin activation. Biochimica et Biophysica Acta. General Subjects, 1865(6), 129894. (doi: 10.1016/j.bbagen.2021.129894) (PMID:33753174)
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Abstract
Parkin and phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) constitute a feed-forward signalling pathway that mediates autophagic removal of damaged mitochondria (mitophagy). With over 130 mutations identified to date in over 1000 patients with early onset parkinsonism, Parkin is considered a hot spot of signalling pathways involved in PD aetiology. Parkin is an E3 ligase and how its activity is regulated has been extensively studied: inter-domain interactions exert a tight inhibition on Parkin activity; binding to phospho-ubiquitin relieves this auto-inhibition; and phosphorylation of Parkin shifts the equilibrium towards maximal Parkin activation. This review focusses on recent, structural findings on the regulation of Parkin activity. What follows is a mechanistic introduction to the family of E3 ligases that includes Parkin, followed by a brief description of structural elements unique to Parkin that lock the enzyme in an autoinhibited state, contrasted with emerging models that have shed light on possible mechanisms of Parkin activation.
| Item Type: | Articles |
|---|---|
| Additional Information: | GSS was funded by Canadian Institutes of Health Research (CIHR) - PJT-166019. HW was funded by Wellcome Trust Investigator Award (209347/Z/17/Z) |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Salzano, Dr Giulia and Tadayon, Dr Roya and Gundogdu, Dr Mehmet and Walden, Professor Helen |
| Authors: | Gundogdu, M., Tadayon, R., Salzano, G., Shaw, G. S., and Walden, H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Biochimica et Biophysica Acta. General Subjects |
| Publisher: | Elsevier |
| ISSN: | 0304-4165 |
| ISSN (Online): | 1872-8006 |
| Published Online: | 20 March 2021 |
| Copyright Holders: | Copyright © 2021 The Authors |
| First Published: | First published in Biochimica et Biophysica Acta. General Subjects 1865(6):129894 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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