RGD Reference Report - The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. - Rat Genome Database

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The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy.

Authors: Bingol, Baris  Tea, Joy S  Phu, Lilian  Reichelt, Mike  Bakalarski, Corey E  Song, Qinghua  Foreman, Oded  Kirkpatrick, Donald S  Sheng, Morgan 
Citation: Bingol B, etal., Nature. 2014 Jun 19;510(7505):370-5. doi: 10.1038/nature13418. Epub 2014 Jun 4.
RGD ID: 13208875
Pubmed: PMID:24896179   (View Abstract at PubMed)
DOI: DOI:10.1038/nature13418   (Journal Full-text)

Cells maintain healthy mitochondria by degrading damaged mitochondria through mitophagy; defective mitophagy is linked to Parkinson's disease. Here we report that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy driven by the ubiquitin ligase parkin (also known as PARK2) and protein kinase PINK1, which are encoded by two genes associated with Parkinson's disease. Parkin ubiquitinates and tags damaged mitochondria for clearance. Overexpression of USP30 removes ubiquitin attached by parkin onto damaged mitochondria and blocks parkin's ability to drive mitophagy, whereas reducing USP30 activity enhances mitochondrial degradation in neurons. Global ubiquitination site profiling identified multiple mitochondrial substrates oppositely regulated by parkin and USP30. Knockdown of USP30 rescues the defective mitophagy caused by pathogenic mutations in parkin and improves mitochondrial integrity in parkin- or PINK1-deficient flies. Knockdown of USP30 in dopaminergic neurons protects flies against paraquat toxicity in vivo, ameliorating defects in dopamine levels, motor function and organismal survival. Thus USP30 inhibition is potentially beneficial for Parkinson's disease by promoting mitochondrial clearance and quality control.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Usp30Ratnegative regulation of mitophagy  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Usp30  (ubiquitin specific peptidase 30)


Additional Information