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Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL
PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. It has been found to work in the same pathway as the E3 ligase Parkin in the maintenance of flight muscles and dopaminergic neurons in Drosophila melanogaster and to recruit cytosolic Parkin to mitochondria to med...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995166/ https://www.ncbi.nlm.nih.gov/pubmed/21115803 http://dx.doi.org/10.1083/jcb.201008084 |
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author | Jin, Seok Min Lazarou, Michael Wang, Chunxin Kane, Lesley A. Narendra, Derek P. Youle, Richard J. |
author_facet | Jin, Seok Min Lazarou, Michael Wang, Chunxin Kane, Lesley A. Narendra, Derek P. Youle, Richard J. |
author_sort | Jin, Seok Min |
collection | PubMed |
description | PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. It has been found to work in the same pathway as the E3 ligase Parkin in the maintenance of flight muscles and dopaminergic neurons in Drosophila melanogaster and to recruit cytosolic Parkin to mitochondria to mediate mitophagy in mammalian cells. Although PINK1 has a predicted mitochondrial import sequence, its cellular and submitochondrial localization remains unclear in part because it is rapidly degraded. In this study, we report that the mitochondrial inner membrane rhomboid protease presenilin-associated rhomboid-like protein (PARL) mediates cleavage of PINK1 dependent on mitochondrial membrane potential. In the absence of PARL, the constitutive degradation of PINK1 is inhibited, stabilizing a 60-kD form inside mitochondria. When mitochondrial membrane potential is dissipated, PINK1 accumulates as a 63-kD full-length form on the outer mitochondrial membrane, where it can recruit Parkin to impaired mitochondria. Thus, differential localization to the inner and outer mitochondrial membranes appears to regulate PINK1 stability and function. |
format | Text |
id | pubmed-2995166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-29951662011-05-29 Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL Jin, Seok Min Lazarou, Michael Wang, Chunxin Kane, Lesley A. Narendra, Derek P. Youle, Richard J. J Cell Biol Research Articles PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. It has been found to work in the same pathway as the E3 ligase Parkin in the maintenance of flight muscles and dopaminergic neurons in Drosophila melanogaster and to recruit cytosolic Parkin to mitochondria to mediate mitophagy in mammalian cells. Although PINK1 has a predicted mitochondrial import sequence, its cellular and submitochondrial localization remains unclear in part because it is rapidly degraded. In this study, we report that the mitochondrial inner membrane rhomboid protease presenilin-associated rhomboid-like protein (PARL) mediates cleavage of PINK1 dependent on mitochondrial membrane potential. In the absence of PARL, the constitutive degradation of PINK1 is inhibited, stabilizing a 60-kD form inside mitochondria. When mitochondrial membrane potential is dissipated, PINK1 accumulates as a 63-kD full-length form on the outer mitochondrial membrane, where it can recruit Parkin to impaired mitochondria. Thus, differential localization to the inner and outer mitochondrial membranes appears to regulate PINK1 stability and function. The Rockefeller University Press 2010-11-29 /pmc/articles/PMC2995166/ /pubmed/21115803 http://dx.doi.org/10.1083/jcb.201008084 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Jin, Seok Min Lazarou, Michael Wang, Chunxin Kane, Lesley A. Narendra, Derek P. Youle, Richard J. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL |
title | Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL |
title_full | Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL |
title_fullStr | Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL |
title_full_unstemmed | Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL |
title_short | Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL |
title_sort | mitochondrial membrane potential regulates pink1 import and proteolytic destabilization by parl |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995166/ https://www.ncbi.nlm.nih.gov/pubmed/21115803 http://dx.doi.org/10.1083/jcb.201008084 |
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