MassIVE MSV000097910

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LC-MS Dataset of Fumarate Levels and Parkin Post Translational Modifications

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Description

This study investigates the regulatory role of fumarate, a metabolite of the citric acid cycle, in PINK1-Parkin-mediated mitophagy-a process essential for mitochondrial quality control and implicated in Parkinsons disease (PD). We identified post-translational succination modifications on Parkin at cysteine residues 323 and 451, demonstrating that fumarate-mediated succination impairs Parkins mitochondrial localization and E3 ligase activity. Using proteomic LC-MS, we discovered novel succination sites, while metabolomic LC-MS enabled the quantification of fumarate levels in biological samples, including mammalian cells and Drosophila. Functional validation with Parkin knock-in Drosophila models harboring succinatable cysteines revealed PD-like phenotypes upon fumarate accumulation, underscoring the physiological relevance of this modification. Our integrated proteomic and metabolomic approach establishes fumarate as an endogenous modulator of mitophagy and provides new insights into the role of mitochondrial metabolism in PD pathogenesis. [doi:10.25345/C57P8TS0V] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: fumaric acid ; fumarate ; DatasetType:Proteomics ; DatasetType:Metabolomics

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Principal Investigators:
(in alphabetical order) 		Jong-Seo Kim, Seoul National University, Korea
Submitting User: JJY5357
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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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