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PXD056511

PXD056511 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUSP14 inhibition enhances Parkin-independent mitophagy in iNeurons
DescriptionLoss 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.
HostingRepositoryPRIDE
AnnounceDate2024-12-18
AnnouncementXMLSubmission_2024-12-18_15:50:34.855.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD056511
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMiguel Prado
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-10-04 11:43:08ID requested
12024-12-18 15:50:35announced
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 affiliationInstituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
contact emailmiguel.prado@ispasturias.es
lab head
Miguel Prado
contact affiliationHarvard Medical School, Boston, USA Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain (lab head)
contact emailmiguel.prado@ispasturias.es
dataset submitter
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Dataset FTP location
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