eprintid: 10050665
rev_number: 26
eprint_status: archive
userid: 608
dir: disk0/10/05/06/65
datestamp: 2018-06-21 13:56:52
lastmod: 2021-09-18 21:50:35
status_changed: 2018-06-21 13:56:52
type: article
metadata_visibility: show
creators_name: Soutar, MPM
creators_name: Kempthorne, L
creators_name: Miyakawa, S
creators_name: Annuario, E
creators_name: Melandri, D
creators_name: Harley, J
creators_name: O'Sullivan, GA
creators_name: Wray, S
creators_name: Hancock, DC
creators_name: Cookson, MR
creators_name: Downward, J
creators_name: Carlton, M
creators_name: Plun-Favreau, H
title: AKT signalling selectively regulates PINK1 mitophagy in SHSY5Y cells and human iPSC-derived neurons
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
divisions: C08
divisions: D09
note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
abstract: The discovery of mutations within genes associated with autosomal recessive Parkinson's disease allowed for the identification of PINK1/Parkin regulated mitophagy as an important pathway for the removal of damaged mitochondria. While recent studies suggest that AKT-dependent signalling regulates Parkin recruitment to depolarised mitochondria, little is known as to whether this can also regulate PINK1 mitochondrial accumulation and downstream mitophagy. Here, we demonstrate that inhibition of AKT signalling decreases endogenous PINK1 accumulation in response to mitochondria depolarisation, subsequent Parkin recruitment, phosphorylation of ubiquitin, and ultimately mitophagy. Conversely, we show that upon stimulation of AKT signalling via insulin, the mitophagy pathway is increased in SHSY5Y cells. These data suggest that AKT signalling is an upstream regulator of PINK1 accumulation on damaged mitochondria. Importantly, we show that the AKT pathway also regulates endogenous PINK1-dependent mitophagy in human iPSC-derived neurons.
date: 2018-06-11
date_type: published
official_url: https://doi.org/10.1038/s41598-018-26949-6
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1561905
doi: 10.1038/s41598-018-26949-6
pii: 10.1038/s41598-018-26949-6
lyricists_name: Melandri, Daniela
lyricists_name: Plun-Favreau, Helene
lyricists_name: Soutar, Marc
lyricists_name: Wray, Selina
lyricists_id: DMELA56
lyricists_id: HPLUN15
lyricists_id: MSOUT43
lyricists_id: SWRAY93
actors_name: Plun-Favreau, Helene
actors_id: HPLUN15
actors_role: owner
full_text_status: public
publication: Science Reports
volume: 8
number: 1
article_number: 8855
event_location: England
issn: 2045-2322
citation:        Soutar, MPM;    Kempthorne, L;    Miyakawa, S;    Annuario, E;    Melandri, D;    Harley, J;    O'Sullivan, GA;                         ... Plun-Favreau, H; + view all <#>        Soutar, MPM;  Kempthorne, L;  Miyakawa, S;  Annuario, E;  Melandri, D;  Harley, J;  O'Sullivan, GA;  Wray, S;  Hancock, DC;  Cookson, MR;  Downward, J;  Carlton, M;  Plun-Favreau, H;   - view fewer <#>    (2018)    AKT signalling selectively regulates PINK1 mitophagy in SHSY5Y cells and human iPSC-derived neurons.                   Science Reports , 8  (1)    , Article 8855.  10.1038/s41598-018-26949-6 <https://doi.org/10.1038/s41598-018-26949-6>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10050665/1/s41598-018-26949-6.pdf