New ProteomeXchange dataset PXD065210

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https://proteomecentral.proteomexchange.org/dataset/PXD065210

Summary of dataset

Status: new
Identifier: PXD065210
HostingRepository: PRIDE
Species: Saccharomyces cerevisiae (Baker's yeast)
Title: The yeast F-box protein Mfb1 and the human DJ-1 homolog Hsp31 are required for cell survival
Submitter: Ebbing de Jong
LabHead: Xin Jie Chen
Description: Mitochondrial biogenesis requires the import of many nuclear-encoded proteins across the Translocase of Outer Membrane (TOM), and the Translocase of Inner Membrane (TIM) 22 or 23 complexes. Protein import defects cannot only impair mitochondrial function but also cause mitochondrial Precursor Overaccumulation Stress (mPOS) in the cytosol. Recent studies showed that specific mutations in the nuclear-encoded Adenine Nucleotide Translocase 1 (ANT1) cause musculoskeletal and neurological diseases by clogging TOM and TIM22 and inducing mPOS. Here, we found that overexpression of MFB1, encoding the mitochondrial F-box protein 1, suppresses cell growth defect caused by a clogger allele of AAC2, the yeast homolog of Ant1. Disruption of MFB1 synergizes with a clogger allele of aac2 to inhibit cell growth. This is accompanied by increased retention of mitochondrial proteins in the cytosol, suggesting a severe defect in mitochondrial protein import. Proximity-dependent biotin ident
ification (BioID) suggested that Mfb1 may interact with Tom22, a component of the TOM complex. Loss of MFB1 under clogging conditions activates genes encoding cytosolic chaperones including Hsp31. Interestingly, disruption of HSP31 creates a synthetic lethality with protein import clogging under respiring conditions. We propose that Mfb1 functions to maintain mitochondrial protein import competency under clogging conditions, whereas Hsp31 plays an important role in protecting the cytosol against mPOS. Mutations in human mitochondria-associated F-box proteins (e.g., Fbxo7) and the human Hsp31 homolog, DJ-1, are known to cause early-onset Parkinson’s disease. Our work may improve the understanding of how these mutations cause neurodegeneration.

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