Parkin structure and function
Identifieur interne : 000604 ( Main/Exploration ); précédent : 000603; suivant : 000605Parkin structure and function
Auteurs : Marjan Seirafi ; Guennadi Kozlov ; Kalle GehringSource :
- The Febs Journal [ 1742-464X ] ; 2015.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Humans, Mitochondria (enzymology), Mitochondrial Degradation, Molecular Sequence Data, Neurons (enzymology), Parkinson Disease (enzymology), Parkinson Disease (pathology), Protein Transport, Ubiquitin-Protein Ligases (chemistry), Ubiquitin-Protein Ligases (physiology), Ubiquitination.
- MESH :
- chemical , chemistry : Ubiquitin-Protein Ligases.
- enzymology : Mitochondria, Neurons, Parkinson Disease.
- pathology : Parkinson Disease.
- chemical , physiology : Ubiquitin-Protein Ligases.
- Amino Acid Sequence, Animals, Humans, Mitochondrial Degradation, Molecular Sequence Data, Protein Transport, Ubiquitination.
Abstract
Mutations in the parkin or PINK1 genes are the leading cause of the autosomal recessive form of Parkinson’s disease. The gene products, the E3 ubiquitin ligase parkin and the serine/threonine kinase PINK1, are neuroprotective proteins, which act together in a mitochondrial quality control pathway. Here, we review the structure of parkin and mechanisms of its autoinhibition and function as a ubiquitin ligase. We present a model for the recruitment and activation of parkin as a key regulatory step in the clearance of depolarized or damaged mitochondria by autophagy (mitophagy). We conclude with a brief overview of other functions of parkin and considerations for drug discovery in the mitochondrial quality control pathway.
Url:
DOI: 10.1111/febs.13249
PubMed: 25712550
PubMed Central: 4672691
Affiliations:
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The gene products, the E3 ubiquitin ligase parkin and the serine/threonine kinase PINK1, are neuroprotective proteins, which act together in a mitochondrial quality control pathway. Here, we review the structure of parkin and mechanisms of its autoinhibition and function as a ubiquitin ligase. We present a model for the recruitment and activation of parkin as a key regulatory step in the clearance of depolarized or damaged mitochondria by autophagy (mitophagy). We conclude with a brief overview of other functions of parkin and considerations for drug discovery in the mitochondrial quality control pathway.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Venderova, K" uniqKey="Venderova K">K Venderova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Valente, Em" uniqKey="Valente E">EM Valente</name></author><author><name sortKey="Abou Sleiman, Pm" uniqKey="Abou Sleiman P">PM Abou-Sleiman</name></author><author><name sortKey="Caputo, V" uniqKey="Caputo V">V Caputo</name></author><author><name sortKey="Muqit, Mm" uniqKey="Muqit M">MM Muqit</name></author><author><name sortKey="Harvey, K" uniqKey="Harvey K">K Harvey</name></author><author><name sortKey="Gispert, S" uniqKey="Gispert S">S Gispert</name></author><author><name sortKey="Ali, Z" uniqKey="Ali Z">Z Ali</name></author><author><name sortKey="Del Turco, D" uniqKey="Del Turco D">D Del 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uniqKey="Wauters F">F Wauters</name></author><author><name sortKey="Van Humbeeck, C" uniqKey="Van Humbeeck C">C Van Humbeeck</name></author><author><name sortKey="Mandemakers, W" uniqKey="Mandemakers W">W Mandemakers</name></author><author><name sortKey="Koentjoro, B" uniqKey="Koentjoro B">B Koentjoro</name></author><author><name sortKey="Sue, C" uniqKey="Sue C">C Sue</name></author><author><name sortKey="Gevaert, K" uniqKey="Gevaert K">K Gevaert</name></author><author><name sortKey="De Strooper, B" uniqKey="De Strooper B">B De Strooper</name></author><author><name sortKey="Verstreken, P" uniqKey="Verstreken P">P Verstreken</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Gehring, Kalle" sort="Gehring, Kalle" uniqKey="Gehring K" first="Kalle" last="Gehring">Kalle Gehring</name><name sortKey="Kozlov, Guennadi" sort="Kozlov, Guennadi" uniqKey="Kozlov G" first="Guennadi" last="Kozlov">Guennadi Kozlov</name><name sortKey="Seirafi, Marjan" sort="Seirafi, Marjan" uniqKey="Seirafi M" first="Marjan" last="Seirafi">Marjan Seirafi</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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