PXD056511 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | USP14 inhibition enhances Parkin-independent mitophagy in iNeurons |
Description | Loss of proteostasis is well documented during physiological aging and depends on the progressive decline in the activity of two major degradative mechanisms: the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway. This decline in proteostasis is exacerbated in age-associated neurodegenerative diseases, such as Parkinson’s Disease (PD). In PD, patients develop an accumulation of aggregated proteins and dysfunctional mitochondria, which leads to ROS production, neuroinflammation and neurodegeneration. We recently reported that inhibition of the deubiquitinating enzyme USP14, which is known to enhance both the UPS and autophagy, increases lifespan and rescues the pathological phenotype of two Drosophila models of PD. Studies on the effects of USP14 inhibition in mammalian neurons have not yet been conducted. To close this gap, we exploited iNeurons differentiated from human embryonic stem cells (hESCs), and investigated the effect of inhibiting USP14 in these cultured neurons. Quantitative global proteomics analysis performed following genetic ablation or pharmacological inhibition of USP14 demonstrated that USP14 loss of function specifically promotes mitochondrial autophagy in iNeurons. Biochemical and imaging data also showed that USP14 inhibition enhances mitophagy. The mitophagic effect of USP14 inhibition proved to be PINK1/Parkin- independent, instead relying on expression of the mitochondrial E3 Ubiquitin Ligase MITOL/MARCH5. Notably, USP14 inhibition normalized the mitochondrial defects of Parkin KO human neurons. |
HostingRepository | PRIDE |
AnnounceDate | 2024-12-18 |
AnnouncementXML | Submission_2024-12-18_15:50:34.855.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD056511 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Miguel Prado |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-10-04 11:43:08 | ID requested | |
⏵ 1 | 2024-12-18 15:50:35 | announced | |
Publication List
Bernardo G, Prado MA, Dashtmian AR, Favaro M, Mauri S, Borsetto A, Marchesan E, Paulo JA, Gygi SP, Finley DJ, Ziviani E, USP14 inhibition enhances Parkin-independent mitophagy in iNeurons. Pharmacol Res, 210():107484(2024) [pubmed] |
10.6019/PXD056511; |
10.1016/j.phrs.2024.107484; |
Keyword List
submitter keyword: USP14, Mitophagy, Autophagy, UPS, Parkin, MARCH5/MITOL, PINK1 |
Contact List
Miguel Prado |
contact affiliation | Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain |
contact email | miguel.prado@ispasturias.es |
lab head | |
Miguel Prado |
contact affiliation | Harvard Medical School, Boston, USA Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain (lab head) |
contact email | miguel.prado@ispasturias.es |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD056511
- Label: PRIDE project
- Name: USP14 inhibition enhances Parkin-independent mitophagy in iNeurons